Mechanisms and significance of bacterial resistance to human cationic antimicrobial peptides

Antimicrobial Peptides and Innate Immunity

Volumn , Issue , 2013, Pages 219-254

  Goytia, Maira ^a   Kandler, Justin L ^a   Shafer, William M ^a,b  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b ATLANTA VA MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85019782375     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-3-0348-0541-4_9     Document Type: Chapter

References (205)

1. Abachin E, Poyart C, Pellegrini E, Milohanic E, Fiedler F, Berche P, Trieu-Cuot P (2002) Formation of D-alanyl-lipoteichoic acid is required for adhesion and virulence of Listeria monocytogenes. Mol Microbiol 43(1):1-14
2. Akesson P, Sjoholm AG, Bjorck L (1996) Protein SIC, a novel extracellular protein of Streptococcus pyogenes interfering with complement function. J Biol Chem 271(2):1081-1088
3. Amer LS, Bishop BM, van Hoek ML (2010) Antimicrobial and antibiofilm activity of cathelicidins and short, synthetic peptides against Francisella. Biochem Biophys Res Commun 396 (2):246-251. doi:S0006-291X(10)00742-4 [pii]10.1016/j.bbrc.2010.04.073
4. Anderl JN, Franklin MJ, Stewart PS (2000) Role of antibiotic penetration limitation in Klebsiella pneumoniae biofilm resistance to ampicillin and ciprofloxacin. Antimicrob Agents Chemother 44(7):1818-1824
5. Bader MW, Sanowar S, Daley ME, Schneider AR, Cho U, Xu W, Klevit RE, Le Moual H, Miller SI (2005) Recognition of antimicrobial peptides by a bacterial sensor kinase. Cell 122(3):461-472. doi:S0092-8674(05)00553-2 [pii]10.1016/j.cell.2005.05.030
6. Banemann A, Deppisch H, Gross R (1998) The lipopolysaccharide of Bordetella bronchiseptica acts as a protective shield against antimicrobial peptides. Infect Immun 66(12):5607-5612
7. Bauer ME, Spinola SM (2000) Localization of Haemophilus ducreyi at the pustular stage of disease in the human model of infection. Infect Immun 68(4):2309-2314
8. Bauer ME, Townsend CA, Ronald AR, Spinola SM (2006) Localization of Haemophilus ducreyi in naturally acquired chancroidal ulcers. Microbes Infect 8(9-10):2465-2468. doi:S1286-4579 (06)00230-9 [pii]10.1016/j.micinf.2006.06.001
9. Bayer AS, Prasad R, Chandra J, Koul A, Smriti M, Varma A, Skurray RA, Firth N, Brown MH, Koo SP, Yeaman MR (2000) In vitro resistance of Staphylococcus aureus to thrombin-induced platelet microbicidal protein is associated with alterations in cytoplasmic membrane fluidity. Infect Immun 68(6):3548-3553
10. Bayer AS, Kupferwasser LI, Brown MH, Skurray RA, Grkovic S, Jones T, Mukhopadhay K, Yeaman MR (2006) Low-level resistance of Staphylococcus aureus to thrombin-induced platelet microbicidal protein 1 in vitro associated with qacA gene carriage is independent of multidrug efflux pump activity. Antimicrob Agents Chemother 50(7):2448-2454. doi:50/7/2448 [pii]10.1128/AAC.00028-06
11. Beceiro A, Llobet E, Aranda J, Bengoechea JA, Doumith M, Hornsey M, Dhanji H, Chart H, Bou G, Livermore DM, Woodford N (2011) Phosphoethanolamine modification of lipid A in colistin-resistant variants of Acinetobacter baumannii mediated by the pmrAB two-component regulatory system. Antimicrob Agents Chemother 55(7):3370-3379. doi:AAC.00079-11 [pii] 10.1128/AAC.00079-11
12. Becker MN, Diamond G, Verghese MW, Randell SH (2000) CD14-dependent lipopolysaccharide- induced beta-defensin-2 expression in human tracheobronchial epithelium. J Biol Chem 275(38):29731-29736. doi:10.1074/jbc.M000184200M000184200 [pii]
13. Belas R, Manos J, Suvanasuthi R (2004) Proteus mirabilis ZapA metalloprotease degrades a broad spectrum of substrates, including antimicrobial peptides. Infect Immun 72(9):5159-5167. doi:10.1128/IAI.72.9.5159-5167.2004
14. Bengoechea JA, Skumik M (2000) Temperature-regulated efflux pump/potassium antiporter system mediates resistance to cationic antimicrobial peptides in Yersinia. Mol Microbiol 37(1):67-80. doi:mmil956 [pii]
15. Bergman P, Johansson L, Asp V, Plant L, Gudmundsson GH, Jonsson AB, Agerberth B (2005) Neisseria gonorrhoeae downregulates expression of the human antimicrobial peptide LL-37. Cell Microbiol 7(7):1009-1017. doi:CMI530 [pii]10.1111/j.1462-5822.2005.00530.x
16. Bernard R, Guiseppi A, Chippaux M, Foglino M, Denizot F (2007) Resistance to bacitracin in Bacillus subtilis: unexpected requirement of the BceAB ABC transporter in the control of expression of its own structural genes. J Bacteriol 189(23):8636-8642. doi:JB.01132-07 [pii] 10.1128/JB.01132-07
17. Bessalle R, Kapitkovsky A, Gorea A, Shalit I, Fridkin M (1990) All-D-magainin: chirality, antimicrobial activity and proteolytic resistance. FEBS Lett 274(1-2):151-155
18. Braff MH, Jones AL, Skerrett SJ, Rubens CE (2007) Staphylococcus aureus exploits cathelicidin antimicrobial peptides produced during early pneumonia to promote staphylokinase-dependent fibrinolysis. J Infect Dis 195(9):1365-1372. doi:JID37442 [pii]10.1086/513277
19. Brogden KA (2005) Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol 3(3):238-250. doi:10.1038/nrmicro1098 [pii] nrmicro1098
20. Brown KL, Hancock RE (2006) Cationic host defense (antimicrobial) peptides. Curr Opin Immunol 18(1):24-30. doi:S0952-7915(05)00199-8 [pii]10.1016/j.coi.2005.11.004
21. Burlak C, Hammer CH, Robinson MA, Whitney AR, McGavin MJ, Kreiswirth BN, Deleo FR (2007) Global analysis of community-associated methicillin-resistant Staphylococcus aureus exoproteins reveals molecules produced in vitro and during infection. Cell Microbiol 9(5):1172-1190. doi: 10.1111/j.1462-5822.2006.00858.x
22. Campos MA, Vargas MA, Regueiro V, Llompart CM, Alberti S, Bengoechea JA (2004) Capsule polysaccharide mediates bacterial resistance to antimicrobial peptides. Infect Immun 72(12):7107-7114. doi:72/12/7107 [pii]10.1128/IAI.72.12.7107-7114.2004
23. 2-independent antimicrobial proteins from human polymorphonuclear granulocytes. Infect Immun 47(2):401-407
24. Collins LV, Kristian SA, Weidenmaier C, Faigle M, Van Kessel KP, Van Strijp JA, Gotz F, Neumeister B, Peschel A (2002) Staphylococcus aureus strains lacking D-alanine modifications of teichoic acids are highly susceptible to human neutrophil killing and are virulence attenuated in mice. J Infect Dis 186(2):214-219. doi:JID010926 [pii]10.1086/341454
25. Cox AD, Wright JC, Li J, Hood DW, Moxon ER, Richards JC (2003) Phosphorylation of the lipid A region of meningococcal lipopolysaccharide: identification of a family of transferases that add phosphoethanolamine to lipopolysaccharide. J Bacteriol 185(11):3270-3277
26. Cramton SE, Gerke C, Schnell NF, Nichols WW, Gotz F (1999) The intercellular adhesion (ica) locus is present in Staphylococcus aureus and is required for biofilm formation. Infect Immun 67(10):5427-5433
27. Cudic M, Otvos L Jr (2002) Intracellular targets of antibacterial peptides. Curr Drug Targets 3(2):101-106
28. Cui L, Lian JQ, Neoh HM, Reyes E, Hiramatsu K (2005) DNA microarray-based identification of genes associated with glycopeptide resistance in Staphylococcus aureus. Antimicrob Agents Chemother 49(8):3404-3413. doi:10.1128/AAC.49.8.3404-3413.2005
29. Cullen TW, Madsen JA, Ivanov PL, Brodbelt JS, Trent MS (2012) Characterization of unique modification of flagellar rod protein FlgG by Campylobacter jejuni lipid A phosphoetha- nolamine transferase, linking bacterial locomotion and antimicrobial peptide resistance. J Biol Chem 287(5):3326-3336. doi:10.1074/jbc.M111.321737
30. de la Fuente-Nunez C, Korolik V, Bains M, Nguyen U, Breidenstein EB, Horsman S, Lewenza S, Burrows L, Hancock RE (2012) Inhibition of bacterial biofilm formation and swarming motility by a small synthetic cationic peptide. Antimicrob Agents Chemother. 56(5): 2696-704. doi:10.1128/AAC.00064-12
31. Dean SN, Bishop BM, van Hoek ML (2011) Susceptibility of Pseudomonas aeruginosa biofilm to alpha-helical peptides: D-enantiomer of LL-37. Front Microbiol 2:128. doi:10.3389/ fmicb.2011.00128
32. del Castillo FJ, del Castillo I, Moreno F (2001) Construction and characterization of mutations at codon 751 of the Escherichia coli gyrB gene that confer resistance to the antimicrobial peptide microcin B17 and alter the activity of DNA gyrase. J Bacteriol 183(6):2137-2140. doi:10.1128/JB.183.6.2137-2140.2001
33. Dintner S, Staron A, Berchtold E, Petri T, Mascher T, Gebhard S (2011) Coevolution of ABC transporters and two-component regulatory systems as resistance modules against antimicrobial peptides in Firmicutes bacteria. J Bacteriol 193(15):3851-3862. doi:JB.05175-11 [pii] 10.1128/JB.05175-11
34. Dorrer E, Teuber M (1977) Induction of polymyxin resistance in Pseudomonas fluorescens by phosphate limitation. Arch Microbiol 114(1):87-89
35. Dorschner RA, Lopez-Garcia B, Peschel A, Kraus D, Morikawa K, Nizet V, Gallo RL (2006) The mammalian ionic environment dictates microbial susceptibility to antimicrobial defense peptides. FASEB J 20(1):35-42. doi:20/1/35 [pii]10.1096/fj.05-4406com
36. Duval BD, Mathew A, Satola SW, Shafer WM (2010) Altered growth, pigmentation, and antimicrobial susceptibility properties of Staphylococcus aureus due to loss of the major cold shock gene cspB. Antimicrob Agents Chemother 54(6):2283-2290. doi:10.1128/AAC.01786-09
37. Ernst CM, Peschel A (2011) Broad-spectrum antimicrobial peptide resistance by MprF-mediated aminoacylation and flipping of phospholipids. Mol Microbiol 80(2):290-299. doi: 10.1111/ j.1365-2958.2011.07576.x
38. Erwin AL, Smith AL (2007) Nontypeable Haemophilus influenzae: understanding virulence and commensal behavior. Trends Microbiol 15(8):355-362. doi:S0966-842X(07)00109-6 [pii] 10.1016/j.tim.2007.06.004
39. Fan X, Goldfine H, Lysenko E, Weiser JN (2001) The transfer of choline from the host to the bacterial cell surface requires glpQ in Haemophilus influenzae. Mol Microbiol 41(5):1029-1036. doi:mmi2571 [pii]
40. Farley MM, Shafer WM, Spitznagel JK (1987) Antimicrobial binding of a radiolabeled cationic neutrophil granule protein. Infect Immun 55(6):1536-1539
41. Farley MM, Shafer WM, Spitznagel JK (1988) Lipopolysaccharide structure determines ionic and hydrophobic binding of a cationic antimicrobial neutrophil granule protein. Infect Immun 56(6):1589-1592
42. Fields PI, Groisman EA, Heffron F (1989) A Salmonella locus that controls resistance to microbicidal proteins from phagocytic cells. Science 243(4894 Pt 1):1059-1062
43. Flannagan RS, Costo G, Grinstein S (2009) Antimicrobial mechanisms of phagocytes and bacterial evasion strategies. Nat Rev Microbiol 7(5):355-366. doi:10.1038/nrmicro2128
44. Friedrich C, Scott MG, Karunaratne N, Yan H, Hancock RE (1999) Salt-resistant alpha-helical cationic antimicrobial peptides. Antimicrob Agents Chemother 43(7):1542-1548
45. Frigimelica E, Bartolini E, Galli G, Grandi G, Grifantini R (2008) Identification of 2 hypothetical genes involved in Neisseria meningitidis cathelicidin resistance. J Infect Dis 197(8): 1124-1132. doi:10.1086/533456
46. Froehlich BJ, Bates C, Scott JR (2009) Streptococcus pyogenes CovRS mediates growth in iron starvation and in the presence of the human cationic antimicrobial peptide LL-37. J Bacteriol 191(2):673-677. doi:JB.01256-08 [pii]10.1128/JB.01256-08
47. Frosch M, Weisgerber C, Meyer TF (1989) Molecular characterization and expression in Escherichia coli of the gene complex encoding the polysaccharide capsule of Neisseria meningitidis group B. Proc Natl Acad Sci USA 86(5):1669-1673
48. Ganz T (2009) Iron in innate immunity: starve the invaders. Curr Opin Immunol 21(1):63-67. doi: S0952-7915(09)00012-0 [pii]10.1016/j.coi.2009.01.011
49. Gao LY, Laval F, Lawson EH, Groger RK, Woodruff A, Morisaki JH, Cox JS, Daffe M, Brown EJ (2003) Requirement for kasB in Mycobacterium mycolic acid biosynthesis, cell wall impermeability and intracellular survival: implications for therapy. Mol Microbiol 49 (6):1547-1563. doi:3667 [pii]
50. Goytia M, Shafer WM (2010) Polyamines can increase resistance of Neisseria gonorrhoeae to mediators of the innate human host defense. Infect Immun 78(7):3187-3195. doi:IAI.01301-09 [pii]10.1128/IAI.01301-09
51. Groisman EA (2001) The pleiotropic two-component regulatory system PhoP-PhoQ. J Bacteriol 183(6):1835-1842. doi:10.1128/JB.183.6.1835-1842.2001
52. Groisman EA, Chiao E, Lipps CJ, Heffron F (1989) Salmonella typhimuriumphoP virulence gene is a transcriptional regulator. Proc Natl Acad Sci USA 86(18):7077-7081
53. Groisman EA, Parra-Lopez C, Salcedo M, Lipps CJ, Heffron F (1992) Resistance to host antimicrobial peptides is necessary for Salmonella virulence. Proc Natl Acad Sci USA 89(24):11939-11943
54. Guina T, Yi EC, Wang H, Hackett M, Miller SI (2000) A PhoP-regulated outer membrane protease of Salmonella enterica serovar typhimurium promotes resistance to alpha-helical antimicrobial peptides. J Bacteriol 182(14):4077-4086
55. Gunn JS (2008) The Salmonella PmrAB regulon: lipopolysaccharide modifications, antimicrobial peptide resistance and more. Trends Microbiol 16(6):284-290. doi:S0966-842X(08)00105-4 [pii]10.1016/j.tim.2008.03.007
56. Gunn JS, Miller SI (1996) PhoP-PhoQ activates transcription of pmrAB, encoding a two- component regulatory system involved in Salmonella typhimurium antimicrobial peptide resistance. J Bacteriol 178(23):6857-6864
57. Gunn JS, Lim KB, Krueger J, Kim K, Guo L, Hackett M, Miller SI (1998) PmrA-PmrB-regulated genes necessary for 4-aminoarabinose lipid A modification and polymyxin resistance. Mol Microbiol 27(6):1171-1182
58. Guo L, Lim KB, Poduje CM, Daniel M, Gunn JS, Hackett M, Miller SI (1998) Lipid A acylation and bacterial resistance against vertebrate antimicrobial peptides. Cell 95(2):189-198. doi: S0092-8674(00)81750-X [pii]
59. Hale JD, Hancock RE (2007) Alternative mechanisms of action of cationic antimicrobial peptides on bacteria. Expert Rev Anti Infect Ther 5(6):951-959. doi:10.1586/14787210.5.6.951
60. Hancock RE (1997) Peptide antibiotics. Lancet 349(9049):418-422. doi:S0140-6736(97)80051-7 [pii]10.1016/S0140-6736(97)80051-7
61. Hancock RE, McPhee JB (2005) Salmonella's sensor for host defense molecules. Cell 122(3):320-322. doi:S0092-8674(05)00754-3 [pii]10.1016/j.cell.2005.07.023
62. Helander IM, Kilpelainen I, Vaara M (1994) Increased substitution of phosphate groups in lipopolysaccharides and lipid A of the polymyxin-resistant pmrA mutants of Salmonella typhimurium: a 31P-NMR study. Mol Microbiol 11(3):481-487
63. Hiron A, Falord M, Valle J, Debarbouille M, Msadek T (2011) Bacitracin and nisin resistance in Staphylococcus aureus: a novel pathway involving the BraS/BraR two-component system (SA2417/SA2418) and both the BraD/BraE and VraD/VraE ABC transporters. Mol Microbiol. doi:10.1111/j.1365-2958.2011.07735.x
64. Huang HW (2006) Molecular mechanism of antimicrobial peptides: the origin of cooperativity. Biochim Biophys Acta 1758(9):1292-1302. doi:S0005-2736(06)00041-1 [pii]10.1016/j. bbamem.2006.02.001
65. Husain F, Nikaido H (2010) Substrate path in the AcrB multidrug efflux pump of Escherichia coli. Mol Microbiol 78(2):320-330. doi:10.1111/j.1365-2958.2010.07330.x
66. Institute Clinical and Laboratory Standard (2009) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard, vol M07-A8, 8th edn. Clinical and Laboratory Standard Institute, Wayne, PA
67. Islam D, Bandholtz L, Nilsson J, Wigzell H, Christensson B, Agerberth B, Gudmundsson G (2001) Downregulation of bactericidal peptides in enteric infections: a novel immune escape mechanism with bacterial DNA as a potential regulator. Nat Med 7(2):180-185. doi:10.1038/84627
68. Jerse AE, Sharma ND, Simms AN, Crow ET, Snyder LA, Shafer WM (2003) A gonococcal efflux pump system enhances bacterial survival in a female mouse model of genital tract infection. Infect Immun 71(10):5576-5582
69. Jin T, Bokarewa M, Foster T, Mitchell J, Higgins J, Tarkowski A (2004) Staphylococcus aureus resists human defensins by production of staphylokinase, a novel bacterial evasion mechanism. J Immunol 172(2):1169-1176
70. Johansson J, Gudmundsson GH, Rottenberg ME, Berndt KD, Agerberth B (1998) Conformation- dependent antibacterial activity of the naturally occurring human peptide LL-37. J Biol Chem 273(6):3718-3724
71. Johansson L, Thulin P, Sendi P, Hertzen E, Linder A, Akesson P, Low DE, Agerberth B, Norrby- Teglund A (2008) Cathelicidin LL-37 in severe Streptococcus pyogenes soft tissue infections in humans. Infect Immun 76(8):3399-3404. doi:10.1128/IAI.01392-07
72. Johnson CR, Newcombe J, Thorne S, Borde HA, Eales-Reynolds LJ, Gorringe AR, Funnell SG, McFadden JJ (2001) Generation and characterization of a PhoP homologue mutant of Neisseria meningitidis. Mol Microbiol 39(5):1345-1355. doi:mmi2324 [pii]
73. Jones A, Georg M, Maudsdotter L, Jonsson AB (2009) Endotoxin, capsule, and bacterial attachment contribute to Neisseria meningitidis resistance to the human antimicrobial peptide LL-37. J Bacteriol 191(12):3861-3868. doi:JB.01313-08 [pii]10.1128/JB.01313-08
74. Kai-Larsen Y, Luthje P, Chromek M, Peters V, Wang X, Holm A, Kadas L, Hedlund KO, Johansson J, Chapman MR, Jacobson SH, Romling U, Agerberth B, Brauner A (2010) Uropathogenic Escherichia coli modulates immune responses and its curli fimbriae interact with the antimicrobial peptide LL-37. PLoS Pathog 6(7):e1001010. doi:10.1371/journal. ppat.1001010
75. Karbarz MJ, Kalb SR, Cotter RJ, Raetz CR (2003) Expression cloning and biochemical characterization of a Rhizobium leguminosarum lipid A 1-phosphatase. J Biol Chem 278(41): 39269-39279. doi:10.1074/jbc.M305830200M305830200 [pii]
76. Katzif S, Danavall D, Bowers S, Balthazar JT, Shafer WM (2003) The major cold shock gene, cspA, is involved in the susceptibility of Staphylococcus aureus to an antimicrobial peptide of human cathepsin G. Infect Immun 71(8):4304-4312
77. Khuller GK, Subrahmanyam D (1970) On the ornithinyl ester of phosphatidylglycerol of Mycobacterium 607. J Bacteriol 101(2):654-656
78. Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH, Lynfield R, Dumyati G, Townes JM, Craig AS, Zell ER, Fosheim GE, McDougal LK, Carey RB, Fridkin SK (2007) Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 298(15):1763-1771. doi:10.1001/jama.298.15.1763
79. Klotman ME, Rapista A, Teleshova N, Micsenyi A, Jarvis GA, Lu W, Porter E, Chang TL (2008) Neisseria gonorrhoeae-induced human defensins 5 and 6 increase HIV infectivity: role in enhanced transmission. J Immunol 180(9):6176-6185. doi:180/9/6176 [pii]
80. Kocianova S, Vuong C, Yao Y, Voyich JM, Fischer ER, DeLeo FR, Otto M (2005) Key role of poly-gamma-DL-glutamic acid in immune evasion and virulence of Staphylococcus epidermidis. J Clin Invest 115(3):688-694. doi:10.1172/JCI23523
81. Koo SP, Bayer AS, Yeaman MR (2001) Diversity in antistaphylococcal mechanisms among membrane-targeting antimicrobial peptides. Infect Immun 69(8):4916-4922. doi:10.1128/ IAI.69.8.4916-4922.2001
82. Koprivnjak T, Peschel A, Gelb MH, Liang NS, Weiss JP (2002) Role of charge properties of bacterial envelope in bactericidal action of human group IIA phospholipase A2 against Staphylococcus aureus. J Biol Chem 277(49):47636-47644. doi:10.1074/jbc.M205104200M205104200 [pii]
83. Kowalski TJ, Berbari EF, Osmon DR (2005) Epidemiology, treatment, and prevention of community-acquired methicillin-resistant Staphylococcus aureus infections. Mayo Clin Proc 80(9):1201-1207, quiz 1208
84. Kraus D, Herbert S, Kristian SA, Khosravi A, Nizet V, Gotz F, Peschel A (2008) The GraRS regulatory system controls Staphylococcus aureus susceptibility to antimicrobial host defenses. BMC Microbiol 8:85. doi1471-2180-8-85 [pii]10.1186/1471-2180-8-85
85. Kristian SA, Datta V, Weidenmaier C, Kansal R, Fedtke I, Peschel A, Gallo RL, Nizet V (2005) D-alanylation of teichoic acids promotes group a Streptococcus antimicrobial peptide resistance, neutrophil survival, and epithelial cell invasion. J Bacteriol 187(19):6719-6725. doi: 187/19/6719 [pii]10.1128/JB.187.19.6719-6725.2005
86. Kupferwasser LI, Skurray RA, Brown MH, Firth N, Yeaman MR, Bayer AS (1999) Plasmidmediated resistance to thrombin-induced platelet microbicidal protein in staphylococci: role of the qacA locus. Antimicrob Agents Chemother 43(10):2395-2399
87. Kuroda M, Kuwahara-Arai K, Hiramatsu K (2000) Identification of the up- and down-regulated genes in vancomycin-resistant Staphylococcus aureus strains Mu3 and Mu50 by cDNA differential hybridization method. Biochem Biophys Res Commun 269(2):485-490. doi:10.1006/bbrc.2000.2277
88. Laarman AJ, Ruyken M, Malone CL, van Strijp JA, Horswill AR, Rooijakkers SH (2011) Staphylococcus aureus metalloprotease aureolysin cleaves complement C3 to mediate immune evasion. J Immunol 186(11):6445-6453. doi:jimmunol.1002948 [pii]10.4049/jimmunol.1002948
89. Lai Y, Villaruz AE, Li M, Cha DJ, Sturdevant DE, Otto M (2007) The human anionic antimicrobial peptide dermcidin induces proteolytic defence mechanisms in staphylococci. Mol Microbiol 63(2):497-506. doi:MMI5540 [pii]10.1111/j.1365-2958.2006.05540.x
90. Lauth X, von Kockritz-Blickwede M, McNamara CW, Myskowski S, Zinkernagel AS, Beall B, Ghosh P, Gallo RL, Nizet V (2009) M1 protein allows Group A streptococcal survival in phagocyte extracellular traps through cathelicidin inhibition. J Innate Immun 1(3):202-214. doi:10.1159/000203645
91. Lee H, Hsu FF, Turk J, Groisman EA (2004) The PmrA-regulated pmrC gene mediates phosphoethanolamine modification of lipid A and polymyxin resistance in Salmonella enterica. J Bacteriol 186(13):4124-4133. doi:10.1128/JB.186.13.4124-4133.2004186/13/ 4124 [pii]
92. Lehrer RI, Ganz T, Selsted ME (1988) Oxygen-independent bactericidal systems-mechanisms and disorders. Hematol Oncol Clin North Am 2(1):159-169
93. Leid JG, Shirtliff ME, Costerton JW, Stoodley P (2002) Human leukocytes adhere to, penetrate, and respond to Staphylococcus aureus biofilms. Infect Immun 70(11):6339-6345
94. Lewenza S, Falsafi RK, Winsor G, Gooderham WJ, McPhee JB, Brinkman FS, Hancock RE (2005) Construction of a mini-Tn5-luxCDABE mutant library in Pseudomonas aeruginosa PAO1: a tool for identifying differentially regulated genes. Genome Res 15(4):583-589. doi:15/4/583 [pii]10.1101/gr.3513905
95. Lewis LA, Choudhury B, Balthazar JT, Martin LE, Ram S, Rice PA, Stephens DS, Carlson R, Shafer WM (2009) Phosphoethanolamine substitution of lipid A and resistance of Neisseria gonorrhoeae to cationic antimicrobial peptides and complement-mediated killing by normal human serum. Infect Immun 77(3):1112-1120. doi:IAI.01280-08 [pii]10.1128/IAI.01280-08
96. Li M, Cha DJ, Lai Y, Villaruz AE, Sturdevant DE, Otto M (2007a) The antimicrobial peptidesensing system aps of Staphylococcus aureus. Mol Microbiol 66(5):1136-1147. doi:MMI5986 [pii]10.1111/j.1365-2958.2007.05986.x
97. Li M, Lai Y, Villaruz AE, Cha DJ, Sturdevant DE, Otto M (2007b) Gram-positive three- component antimicrobial peptide-sensing system. Proc Natl Acad Sci USA 104(22): 9469-9474. doi:0702159104 [pii]10.1073/pnas.0702159104
98. Lin J, Wang Y, Hoang KV (2009) Systematic identification of genetic loci required for polymyxin resistance in Campylobacter jejuni using an efficient in vivo transposon mutagenesis system. Foodborne Pathog Dis 6(2):173-185. doi:10.1089/fpd.2008.0177
99. Llobet E, Tomas JM, Bengoechea JA (2008) Capsule polysaccharide is a bacterial decoy for antimicrobial peptides. Microbiology 154(Pt 12):3877-3886. doi:154/12/3877 [pii]10.1099/ mic.0.2008/022301-0
100. Lomovskaya O, Bostian KA (2006) Practical applications and feasibility of efflux pump inhibitors in the clinic-a vision for applied use. Biochem Pharmacol 71(7):910-918. doi:S0006-2952(05) 00815-4 [pii]10.1016/j.bcp. 2005.12.008
101. Lysenko ES, Gould J, Bals R, Wilson JM, Weiser JN (2000) Bacterial phosphorylcholine decreases susceptibility to the antimicrobial peptide LL-37/hCAP18 expressed in the upper respiratory tract. Infect Immun 68(3):1664-1671
102. Macfarlane EL, Kwasnicka A, Ochs MM, Hancock RE (1999) PhoP-PhoQ homologues in Pseudomonas aeruginosa regulate expression of the outer-membrane protein OprH and polymyxin B resistance. Mol Microbiol 34(2):305-316. doi:mmi1600 [pii]
103. Macfarlane EL, Kwasnicka A, Hancock RE (2000) Role of Pseudomonas aeruginosa PhoP-PhoQ in resistance to antimicrobial cationic peptides and aminoglycosides. Microbiology 146(Pt 10): 2543-2554
104. Madan R, Rastogi R, Parashuraman S, Mukhopadhyay A (2012) Salmonella acquires lysosome- associated membrane protein 1 (LAMP1) on phagosomes from golgi via SipC proteinmediated recruitment of host Syntaxin6. J Biol Chem 287(8):5574-5587. doi:10.1074/jbc. M111.286120
105. Mah TF, Pitts B, Pellock B, Walker GC, Stewart PS, O'Toole GA (2003) A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance. Nature 426(6964):306-310. doi:10.1038/nature02122nature02122 [pii]
106. Maloney E, Stankowska D, Zhang J, Fol M, Cheng QJ, Lun S, Bishai WR, Rajagopalan M, Chatterjee D, Madiraju MV (2009) The two-domain LysX protein of Mycobacterium tuberculosis is required for production of lysinylated phosphatidylglycerol and resistance to cationic antimicrobial peptides. PLoS Pathog 5(7):e1000534. doi:10.1371/journal.ppat.1000534
107. Mandin P, Fsihi H, Dussurget O, Vergassola M, Milohanic E, Toledo-Arana A, Lasa I, Johansson J, Cossart P (2005) VirR, a response regulator critical for Listeria monocytogenes virulence. Mol Microbiol 57(5):1367-1380. doi:MMI4776 [pii]10.1111/j.1365-2958.2005.04776.x
108. Marra MN, Wilde CG, Griffith JE, Snable JL, Scott RW (1990) Bactericidal/permeability- increasing protein has endotoxin-neutralizing activity. J Immunol 144(2):662-666
109. Mason KM, Munson RS Jr, Bakaletz LO (2005) A mutation in the sap operon attenuates survival of nontypeable Haemophilus influenzae in a chinchilla model of otitis media. Infect Immun 73(1):599-608. doi:73/1/599 [pii]10.1128/IAI.73.1.599-608.2005
110. Mason KM, Bruggeman ME, Munson RS, Bakaletz LO (2006) The non-typeable Haemophilus influenzae Sap transporter provides a mechanism of antimicrobial peptide resistance and SapD- dependent potassium acquisition. Mol Microbiol 62(5):1357-1372. doi:MMI5460 [pii] 10.1111/j.1365-2958.2006.05460.x
111. Mason KM, Raffel FK, Ray WC, Bakaletz LO (2011) Heme utilization by nontypeable Haemophilus influenzae is essential and dependent on Sap transporter function. J Bacteriol 193(10):2527-2535. doi:JB.01313-10 [pii]10.1128/JB.01313-10
112. Matson JS, Yoo HJ, Hakansson K, Dirita VJ (2010) Polymyxin B resistance in El Tor Vibrio cholerae requires lipid acylation catalyzed by MsbB. J Bacteriol 192(8):2044-2052. doi: JB.00023-10 [pii]10.1128/JB.00023-10
113. McCoy AJ, Liu H, Falla TJ, Gunn JS (2001) Identification of Proteus mirabilis mutants with increased sensitivity to antimicrobial peptides. Antimicrob Agents Chemother 45(7): 2030-2037. doi:10.1128/AAC.45.7.2030-2037.2001
114. McNabb SJ, Jajosky RA, Hall-Baker PA, Adams DA, Sharp P, Worshams C, Anderson WJ, Javier AJ, Jones GJ, Nitschke DA, Rey A, Wodajo MS (2008) Summary of notifiable diseases-United States, 2006. MMWR Morb Mortal Wkly Rep 55(53):1-92. doi:mm5553a1 [pii]
115. McPhee JB, Lewenza S, Hancock RE (2003) Cationic antimicrobial peptides activate a two- component regulatory system, PmrA-PmrB, that regulates resistance to polymyxin B and cationic antimicrobial peptides in Pseudomonas aeruginosa. Mol Microbiol 50(1):205-217. doi:3673 [pii]
116. Messner P, Steiner K, Zarschler K, Schaffer C (2008) S-layernanoglycobiology of bacteria. Carbohydr Res 343(12):1934-1951. doi:S0008-6215(08)00004-9 [pii]10.1016/j.carres.2007.12.025
117. Miller SI, Kukral AM, Mekalanos JJ (1989) A two-component regulatory system (phoP phoQ) controls Salmonella typhimurium virulence. Proc Natl Acad Sci USA 86(13):5054-5058
118. Miller SI, Pulkkinen WS, Selsted ME, Mekalanos JJ (1990) Characterization of defensin resistance phenotypes associated with mutations in the phoP virulence regulon of Salmonella typhimurium. Infect Immun 58(11):3706-3710
119. Mishra NN, Liu GY, Yeaman MR, Nast CC, Proctor RA, McKinnell J, Bayer AS (2011) Carotenoid-related alteration of cell membrane fluidity impacts Staphylococcus aureus susceptibility to host defense peptides. Antimicrob Agents Chemother 55(2):526-531. doi: AAC.00680-10 [pii]10.1128/AAC.00680-10
120. Moranta D, Regueiro V, March C, Llobet E, Margareto J, Larrarte E, Garmendia J, Bengoechea JA (2010) Klebsiella pneumoniae capsule polysaccharide impedes the expression of beta- defensins by airway epithelial cells. Infect Immun 78(3):1135-1146. doi:IAI.00940-09 [pii] 10.1128/IAI.00940-09
121. Moskowitz SM, Ernst RK, Miller SI (2004) PmrAB, a two-component regulatory system of Pseudomonas aeruginosa that modulates resistance to cationic antimicrobial peptides and addition of aminoarabinose to lipid A. J Bacteriol 186(2):575-579
122. Mount KL, Townsend CA, Rinker SD, Gu X, Fortney KR, Zwickl BW, Janowicz DM, Spinola SM, Katz BP, Bauer ME (2010) Haemophilus ducreyi SapA contributes to cathelicidin resistance and virulence in humans. Infect Immun 78(3):1176-1184. doi:IAI.01014-09 [pii] 10.1128/IAI.01014-09
123. Mulcahy H, Charron-Mazenod L, Lewenza S (2008) Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms. PLoS Pathog 4(11): e1000213. doi:10.1371/journal.ppat.1000213
124. Murakami S, Nakashima R, Yamashita E, Matsumoto T, Yamaguchi A (2006) Crystal structures of a multidrug transporter reveal a functionally rotating mechanism. Nature 443(7108): 173-179. doi:nature05076 [pii]10.1038/nature05076
125. Nahaie MR, Goodfellow M, Minnikin DE, Hajek V (1984) Polar lipid and isoprenoid quinone composition in the classification of Staphylococcus. J Gen Microbiol 130(9):2427-2437
126. Navarre WW, Halsey TA, Walthers D, Frye J, McClelland M, Potter JL, Kenney LJ, Gunn JS, Fang FC, Libby SJ (2005) Co-regulation of Salmonella enterica genes required for virulence and resistance to antimicrobial peptides by SlyA and PhoP/PhoQ. Mol Microbiol 56 (2):492-508. doi:MMI4553 [pii]10.1111/j.1365-2958.2005.04553.x
127. Neuhaus FC, Baddiley J (2003) A continuum of anionic charge: structures and functions of D-alanyl-teichoic acids in gram-positive bacteria. Microbiol Mol Biol Rev 67(4):686-723
128. Newcombe J, Eales-Reynolds LJ, Wootton L, Gorringe AR, Funnell SG, Taylor SC, McFadden JJ (2004) Infection with an avirulent phoP mutant of Neisseria meningitidis confers broad crossreactive immunity. Infect Immun 72(1):338-344
129. Nishi H, Komatsuzawa H, Fujiwara T, McCallum N, Sugai M (2004) Reduced content of lysyl- phosphatidylglycerol in the cytoplasmic membrane affects susceptibility to moenomycin, as well as vancomycin, gentamicin, and antimicrobial peptides, in Staphylococcus aureus. Antimicrob Agents Chemother 48(12):4800-4807. doi:48/12/4800 [pii]10.1128/AAC.48.12.4800-4807.2004
130. Nizet V, Gallo RL (2002) Surviving innate immunity. Trends Microbiol 10(8):358-359
131. Nuding S, Zabel LT, Enders C, Porter E, Fellermann K, Wehkamp J, Mueller HA, Stange EF (2009) Antibacterial activity of human defensins on anaerobic intestinal bacterial species: a major role of HBD-3. Microbes Infect 11(3):384-393. doi:S1286-4579(09)00004-5 [pii] 10.1016/j.micinf.2009.01.001
132. Nyberg P, Rasmussen M, Bjorck L (2004) Alpha2-macroglobulin-proteinase complexes protect Streptococcus pyogenes from killing by the antimicrobial peptide LL-37. J Biol Chem 279 (51):52820-52823. doi:C400485200 [pii]10.1074/jbc.C400485200
133. Ohnishi M, Golparian D, Shimuta K, Saika T, Hoshina S, Iwasaku K, Nakayama S, Kitawaki J, Unemo M (2011) Is Neisseria gonorrhoeae Initiating a future era of untreatable gonorrhea?: detailed characterization of the first strain with high-level resistance to ceftriaxone. Antimicrob Agents Chemother 55(7):3538-3545. doi:AAC.00325-11 [pii]10.1128/AAC.00325-11
134. Otto M (2009) Bacterial sensing of antimicrobial peptides. Contrib Microbiol 16:136-149. doi:000219377 [pii]10.1159/000219377
135. Otto M, Peschel A, Gotz F (1998) Producer self-protection against the lantibiotic epidermin by the ABC transporter EpiFEG of Staphylococcus epidermidis Tu3298. FEMS Microbiol Lett 166 (2):203-211. doi:S0378109798003334 [pii]
136. Ouyang J, Tian XL, Versey J, Wishart A, Li YH (2010) The BceABRS four-component system regulates the bacitracin-induced cell envelope stress response in Streptococcus mutans. Antimicrob Agents Chemother 54(9):3895-3906. doi:AAC.01802-09 [pii]10.1128/AAC.01802-09
137. Overhage J, Campisano A, Bains M, Torfs EC, Rehm BH, Hancock RE (2008) Human host defense peptide LL-37 prevents bacterial biofilm formation. Infect Immun 76(9):4176-4182. doi:10.1128/IAI.00318-08IAI.00318-08 [pii]
138. Padilla E, Llobet E, Domenech-Sanchez A, Martinez-Martinez L, Bengoechea JA, Alberti S (2010) Klebsiella pneumoniae AcrAB efflux pump contributes to antimicrobial resistance and virulence. Antimicrob Agents Chemother 54(1):177-183. doi:AAC.00715-09 [pii] 10.1128/AAC.00715-09
139. Park PW, Pier GB, Hinkes MT, Bernfield M (2001) Exploitation of syndecan-1 shedding by Pseudomonas aeruginosa enhances virulence. Nature 411(6833):98-102. doi:10.1038/ 3507510035075100 [pii]
140. Parra-Lopez C, Baer MT, Groisman EA (1993) Molecular genetic analysis of a locus required for resistance to antimicrobial peptides in Salmonella typhimurium. EMBO J 12(11):4053-4062
141. Pence MA, Rooijakkers SH, Cogen AL, Cole JN, Hollands A, Gallo RL, Nizet V (2010) Streptococcal inhibitor of complement promotes innate immune resistance phenotypes of invasive M1T1 group A Streptococcus. J Innate Immun 2(6):587-595. doi:000317672 [pii] 10.1159/000317672
142. Peschel A (2002) How do bacteria resist human antimicrobial peptides? Trends Microbiol 10(4):179-186. doi:S0966842X02023338 [pii]
143. Peschel A, Sahl HG (2006) The co-evolution of host cationic antimicrobial peptides and microbial resistance. Nat Rev Microbiol 4(7):529-536. doi:nrmicro1441 [pii]10.1038/nrmicro1441
144. Peschel A, Otto M, Jack RW, Kalbacher H, Jung G, Gotz F (1999) Inactivation of the dlt operon in Staphylococcus aureus confers sensitivity to defensins, protegrins, and other antimicrobial peptides. J Biol Chem 274(13):8405-8410
145. Peschel A, Vuong C, Otto M, Gotz F (2000) The D-alanine residues of Staphylococcus aureus teichoic acids alter the susceptibility to vancomycin and the activity of autolytic enzymes. Antimicrob Agents Chemother 44(10):2845-2847
146. Peschel A, Jack RW, Otto M, Collins LV, Staubitz P, Nicholson G, Kalbacher H, Nieuwenhuizen WF, Jung G, Tarkowski A, van Kessel KP, van Strijp JA (2001) Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with L-lysine. J Exp Med 193(9):1067-1076
147. Piddock LJ (2006) Multidrug-resistance efflux pumps-not just for resistance. Nat Rev Microbiol 4(8):629-636. doi:nrmicro1464 [pii]10.1038/nrmicro1464
148. Prost LR, Miller SI (2008) The Salmonellae PhoQ sensor: mechanisms of detection of phagosome signals. Cell Microbiol 10(3):576-582. doi:CMI1111 [pii]10.1111/j.1462-5822.2007.01111.x
149. Qu X-D, Harwig SSL, Oren A, Shafer WM, Lehrer RI (1996) Susceptibility of Neisseria gonorrhoeae to protegrins. Infect Immun 64(4):1240-1245
150. Ray K, Marteyn B, Sansonetti PJ, Tang CM (2009) Life on the inside: the intracellular lifestyle of cytosolic bacteria. Nat Rev Microbiol 7(5):333-340. doi:10.1038/nrmicro2112
151. Rest RF, Cooney MH, Spitznagel JK (1977) Susceptibility of lipopolysaccharide mutants to the bactericidal action of human neutrophil lysosomal fractions. Infect Immun 16(1):145-151
152. Rinker SD, Trombley MP, Gu X, Fortney KR, Bauer ME (2011) Deletion of mtrC in Haemophilus ducreyi increases sensitivity to human antimicrobial peptides and activates the CpxRA regulon. Infect Immun 79(6):2324-2334. doi:IAI.01316-10 [pii]10.1128/IAI.01316-10
153. Roland KL, Martin LE, Esther CR, Spitznagel JK (1993) Spontaneous pmrA mutants of Salmonella typhimurium LT2 define a new two-component regulatory system with a possible role in virulence. J Bacteriol 175(13):4154-4164
154. Roland KL, Esther CR, Spitznagel JK (1994) Isolation and characterization of a gene, pmrD, from Salmonella typhimurium that confers resistance to polymyxin when expressed in multiple copies. J Bacteriol 176(12):3589-3597
155. Rouquette C, Harmon JB, Shafer WM (1999) Induction of the mtrCDE-encoded efflux pump system of Neisseria gonorrhoeae requires MtrA, an AraC-like protein. Mol Microbiol 33(3):651-658. doi:mole1517 [pii]
156. Roy H, Ibba M (2008) RNA-dependent lipid remodeling by bacterial multiple peptide resistance factors. Proc Natl Acad Sci USA 105(12):4667-4672. doi:0800006105 [pii]10.1073/ pnas.0800006105
157. Salzman NH, Ghosh D, Huttner KM, Paterson Y, Bevins CL (2003) Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 422(6931): 522-526. doi:10.1038/nature01520nature01520 [pii]
158. Schmidtchen A, Frick IM, Bjorck L (2001) Dermatan sulphate is released by proteinases of common pathogenic bacteria and inactivates antibacterial alpha-defensin. Mol Microbiol 39(3):708-713. doi:mmi2251 [pii]
159. Schmidtchen A, Frick IM, Andersson E, Tapper H, Bjorck L (2002) Proteinases of common pathogenic bacteria degrade and inactivate the antibacterial peptide LL-37. Mol Microbiol 46(1):157-168
160. Schroeder BO, Wu Z, Nuding S, Groscurth S, Marcinowski M, Beisner J, Buchner J, Schaller M, Stange EF, Wehkamp J (2011) Reduction of disulphide bonds unmasks potent antimicrobial activity of human beta-defensin 1. Nature 469(7330):419-423. doi:nature09674 [pii]10.1038/ nature09674
161. Scott CC, Botelho RJ, Grinstein S (2003) Phagosome maturation: a few bugs in the system. J Membr Biol 193(3):137-152. doi:10.1007/s00232-002-2008-2
162. Seib KL, Serruto D, Oriente F, Delany I, Adu-Bobie J, Veggi D, Arico B, Rappuoli R, Pizza M (2009) Factor H-binding protein is important for meningococcal survival in human whole blood and serum and in the presence of the antimicrobial peptide LL-37. Infect Immun 77(1):292-299. doi:IAI.01071-08 [pii]10.1128/IAI.01071-08
163. Shafer WM, Onunka VC (1989) Mechanism of staphylococcal resistance to non-oxidative antimicrobial action of neutrophils: importance of pH and ionic strength in determining the bactericidal action of cathepsin G. J Gen Microbiol 135(4):825-830
164. Shafer WM, Casey SG, Spitznagel JK (1984) Lipid A and resistance of Salmonella typhimurium to antimicrobial granule proteins of human neutrophil granulocytes. Infect Immun 43(3):834-838
165. Shafer WM, Qu X, Waring AJ, Lehrer RI (1998) Modulation of Neisseria gonorrhoeae susceptibility to vertebrate antibacterial peptides due to a member of the resistance/nodulation/division efflux pump family. Proc Natl Acad Sci USA 95(4):1829-1833
166. Shafer WM, Folster JP, Nicholas RA (2010) Molecular mechanisms of antibiotic resistance expressed by the pathogenic Neisseria. In: Genco CA, Wetzler L (eds) Neisseria. Molecular mechanisms of pathogenesis. Caister Academic, Norfolk, pp 245-268
167. Shelton CL, Raffel FK, Beatty WL, Johnson SM, Mason KM (2011) Sap transporter mediated import and subsequent degradation of antimicrobial peptides in Haemophilus. PLoS Pathog 7(11):e1002360. doi:10.1371/journal.ppat.1002360
168. Shprung T, Peleg A, Rosenfeld Y, Trieu-Cuot P, Shai Y (2012) Effect of PhoP-PhoQ activation by broad repertoire of antimicrobial peptides on bacterial resistance. J Biol Chem 287(7):4544-4551. doi:10.1074/jbc.M111.278523
169. Sieprawska-Lupa M, Mydel P, Krawczyk K, Wojcik K, Puklo M, Lupa B, Suder P, Silberring J, Reed M, Pohl J, Shafer W, McAleese F, Foster T, Travis J, Potempa J (2004) Degradation of human antimicrobial peptide LL-37 by Staphylococcus aureus-derived proteinases. Antimicrob Agents Chemother 48(12):4673-4679. doi:48/12/4673 [pii]10.1128/AAC.48.12.4673-4679.2004
170. Silhavy TJ, Kahne D, Walker S (2010) The bacterial cell envelope. Cold Spring Harb Perspect Biol 2(5):a000414. doi:cshperspect.a000414 [pii]10.1101/cshperspect.a000414
171. Singh PK, Schaefer AL, Parsek MR, Moninger TO, Welsh MJ, Greenberg EP (2000) Quorumsensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature 407(6805):762-764. doi:10.1038/35037627
172. Slayden RA, Barry CE 3rd (2002) The role of KasA and KasB in the biosynthesis of meromycolic acids and isoniazid resistance in Mycobacterium tuberculosis. Tuberculosis (Edinb) 82(4-5):149-160. doi:S1472979202903331 [pii]
173. Sochacki KA, Barns KJ, Bucki R, Weisshaar JC (2011) Real-time attack on single Escherichia coli cells by the human antimicrobial peptide LL-37. Proc Natl Acad Sci USA 108(16):E77-E81. doi:10.1073/pnas.1101130108
174. Sorrell TC, Lehrer RI, Cline MJ (1978) Mechanism of nonspecific macrophage-mediated cytotoxicity: evidence for lack of dependence upon oxygen. J Immunol 120(2):347-352
175. Spinola SM, Bong CT, Faber AL, Fortney KR, Bennett SL, Townsend CA, Zwickl BE, Billings SD, Humphreys TL, Bauer ME, Katz BP (2003) Differences in host susceptibility to disease progression in the human challenge model of Haemophilus ducreyi infection. Infect Immun 71(11):6658-6663
176. Spinosa MR, Progida C, Tala A, Cogli L, Alifano P, Bucci C (2007) The Neisseria meningitidis capsule is important for intracellular survival in human cells. Infect Immun 75(7):3594-3603. doi:IAI.01945-06 [pii]10.1128/IAI.01945-06
177. Spitznagel JK (1961) The effects of mammalian and other cationic polypeptides on the cytochem- ical character of bacterial cells. J Exp Med 114:1063-1078
178. Spitznagel JK (1990) Antibiotic proteins of human neutrophils. J Clin Invest 86(5):1381-1386. doi:10.1172/JCI114851
179. Spitznagel JK, Shafer WM (1985) Neutrophil killing of bacteria by oxygen-independent mechanisms: a historical summary. Rev Infect Dis 7(3):398-403
180. Starner TD, Swords WE, Apicella MA, McCray PB Jr (2002) Susceptibility of nontypeable Haemophilus influenzae to human beta-defensins is influenced by lipooligosaccharide acylation. Infect Immun 70(9):5287-5289
181. Staubitz P, Neumann H, Schneider T, Wiedemann I, Peschel A (2004) MprF-mediated biosynthesis of lysylphosphatidylglycerol, an important determinant in staphylococcal defensin resistance. FEMS Microbiol Lett 231(1):67-71. doi:10.1016/S0378-1097(03)00921-2S0378109703009212 [pii].
182. Stephens DS (2009) Biology and pathogenesis of the evolutionarily successful, obligate human bacterium Neisseria meningitidis. Vaccine 27(Suppl 2):B71-B77. doi:S0264-410X(09)00635-5 [pii]10.1016/j.vaccine.2009.04.070
183. Stewart PS, Costerton JW (2001) Antibiotic resistance of bacteria in biofilms. Lancet 358(9276):135-138. doi:S0140673601053211 [pii]
184. Stumpe S, Schmid R, Stephens DL, Georgiou G, Bakker EP (1998) Identification of OmpT as the protease that hydrolyzes the antimicrobial peptide protamine before it enters growing cells of Escherichia coli. J Bacteriol 180(15):4002-4006
185. Symmons MF, Bokma E, Koronakis E, Hughes C, Koronakis V (2009) The assembled structure of a complete tripartite bacterial multidrug efflux pump. Proc Natl Acad Sci USA 106(17):7173-7178. doi:0900693106 [pii]10.1073/pnas.0900693106
186. Tada H, Sugawara S, Nemoto E, Takahashi N, Imamura T, Potempa J, Travis J, Shimauchi H, Takada H (2002) Proteolysis of CD14 on human gingival fibroblasts by arginine-specific cysteine proteinases from Porphyromonas gingivalis leading to down-regulation of lipopolysaccharide-induced interleukin-8 production. Infect Immun 70(6):3304-3307
187. Trent MS (2004) Biosynthesis, transport, and modification of lipid A. Biochem Cell Biol 82(1):71-86. doi:10.1139/o03-070o03-070 [pii]
188. Tzeng YL, Datta A, Ambrose K, Lo M, Davies JK, Carlson RW, Stephens DS, Kahler CM (2004) The MisR/MisS two-component regulatory system influences inner core structure and immunotype of lipooligosaccharide in Neisseria meningitidis. J Biol Chem 279(33): 35053-35062. doi:10.1074/jbc.M401433200M401433200 [pii]
189. Tzeng YL, Ambrose KD, Zughaier S, Zhou X, Miller YK, Shafer WM, Stephens DS (2005) Cationic antimicrobial peptide resistance in Neisseria meningitidis. J Bacteriol 187(15): 5387-5396. doi:187/15/5387-a [pii]10.1128/JB.187.15.5387-5396.2005
190. Uchiya K, Barbieri MA, Funato K, Shah AH, Stahl PD, Groisman EA (1999) A Salmonella virulence protein that inhibits cellular trafficking. EMBO J 18(14):3924-3933. doi:10.1093/ emboj/18.14.3924
191. Ulvatne H, Haukland HH, Samuelsen O, Kramer M, Vorland LH (2002) Proteases in Escherichia coli and Staphylococcus aureus confer reduced susceptibility to lactoferricin B. J antimicrob chemother 50(4):461-467
192. Vaara M, Vaara T, Jensen M, Helander I, Nurminen M, Rietschel ET, Makela PH (1981) Characterization of the lipopolysaccharide from the polymyxin-resistant pmrA mutants of Salmonella typhimurium. FEBS Lett 129(1):145-149
193. Valdivia RH, Falkow S (1997) Fluorescence-based isolation of bacterial genes expressed within host cells. Science 277(5334):2007-2011
194. Vesga O, Groeschel MC, Otten MF, Brar DW, Vann JM, Proctor RA (1996) Staphylococcus aureus small colony variants are induced by the endothelial cell intracellular milieu. J Infect Dis 173(3):739-742
195. Vuong C, Kocianova S, Voyich JM, Yao Y, Fischer ER, DeLeo FR, Otto M (2004) A crucial role for exopolysaccharide modification in bacterial biofilm formation, immune evasion, and virulence. J Biol Chem 279(52):54881-54886. doi:M411374200 [pii]10.1074/jbc.M411374200
196. Wade D, Boman A, Wahlin B, Drain CM, Andreu D, Boman HG, Merrifield RB (1990) All-D amino acid-containing channel-forming antibiotic peptides. Proc Natl Acad Sci USA 87(12): 4761-4765
197. Warner DM, Folster JP, Shafer WM, Jerse AE (2007) Regulation of the MtrC-MtrD-MtrE efflux- pump system modulates the in vivo fitness of Neisseria gonorrhoeae. J Infect Dis 196(12): 1804-1812. doi:10.1086/522964
198. Warner DM, Shafer WM, Jerse AE (2008) Clinically relevant mutations that cause derepression of the Neisseria gonorrhoeae MtrC-MtrD-MtrE Efflux pump system confer different levels of antimicrobial resistance and in vivo fitness. Mol Microbiol 70(2):462-478. doi:MMI6424 [pii] 10.1111/j.1365-2958.2008.06424.x
199. Wehkamp J, Salzman NH, Porter E, Nuding S, Weichenthal M, Petras RE, Shen B, Schaeffeler E, Schwab M, Linzmeier R, Feathers RW, Chu H, Lima H Jr, Fellermann K, Ganz T, Stange EF, Bevins CL (2005) Reduced paneth cell alpha-defensins in ileal Crohn's disease. Proc Natl Acad Sci USA 102(50):18129-18134. doi:0505256102 [pii]10.1073/pnas.0505256102
200. Yeaman MR, Yount NY (2003) Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev 55(1):27-55. doi:10.1124/pr.55.1.2
201. Zahner D, Zhou X, Chancey ST, Pohl J, Shafer WM, Stephens DS (2010) Human antimicrobial peptide LL-37 induces MefE/Mel-mediated macrolide resistance in Streptococcus pneumoniae. Antimicrob Agents Chemother 54(8):3516-3519. doi:10.1128/AAC.01756-09
202. Zeya HI, Spitznagel JK (1966a) Cationic proteins of polymorphonuclear leukocyte lysosomes. I. Resolution of antibacterial and enzymatic activities. J Bacteriol 91(2):750-754
203. Zeya HI, Spitznagel JK (1966b) Cationic proteins of polymorphonuclear leukocyte lysosomes. II. Composition, properties, and mechanism of antibacterial action. J Bacteriol 91(2):755-762
204. Zipfel PF, Reuter M (2009) Complement activation products C3a and C4a as endogenous antimicrobial peptides. Int J Pept Res Th 15(2):87-95. doi:10.1007/s10989-009-9180-5
205. Zughaier SM, Svoboda P, Pohl J, Stephens DS, Shafer WM (2010) The human host defense peptide LL-37 interacts with Neisseria meningitidis capsular polysaccharides and inhibits inflammatory mediators release. PLoS One 5(10):e13627. doi:10.1371/journal.pone.0013627