Staphylococcus aureus pathogenesis in diverse host environments

Pathogens and Disease

Volumn 75, Issue 1, 2017, Pages

  Balasubramanian, Divya ^a   Harper, Lamia ^a   Shopsin, Bo ^a   Torres, Victor J ^a  

^a NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Gene regulation; MRSA; Pathogenesis; Staphylococcus aureus

Indexed keywords

ANTIINFECTIVE AGENT; BRANCHED CHAIN AMINO ACID; CARBOHYDRATE; DIFLUNISAL; IRON; MONOCLONAL ANTIBODY; OXYGEN;

BACTERIAL METABOLISM; BACTERIAL VIRULENCE; GASTROINTESTINAL INFECTION; HOST PATHOGEN INTERACTION; HUMAN; HYPOXIA; NONHUMAN; NUTRIENT LIMITATION; PATHOGENESIS; PRIORITY JOURNAL; SHORT SURVEY; SIGNAL TRANSDUCTION; STAPHYLOCOCCAL SKIN INFECTION; STAPHYLOCOCCUS AUREUS; ANIMAL; DRUG EFFECTS; ENERGY METABOLISM; METABOLISM; MICROBIOLOGY; OXIDATION REDUCTION REACTION; PHYSIOLOGY; QUORUM SENSING; STAPHYLOCOCCUS INFECTION; VIRULENCE;

ANIMALS; ANTI-BACTERIAL AGENTS; ENERGY METABOLISM; HOST-PATHOGEN INTERACTIONS; HUMANS; OXIDATION-REDUCTION; QUORUM SENSING; SIGNAL TRANSDUCTION; STAPHYLOCOCCAL INFECTIONS; STAPHYLOCOCCUS AUREUS; VIRULENCE;

EID: 85028586378     PISSN: None     EISSN: 2049632X     Source Type: Journal    
DOI: 10.1093/femspd/ftx005     Document Type: Short Survey

References (200)

1. American Database Association. Standards of medical care in diabetes. Diabetes Care 2016;39:S39-46
2. Archer NK, Mazaitis MJ, Costerton JW et al. Staphylococcus aureus biofilms: properties, regulation, and roles in human disease. Virulence 2011;2:445-59
3. Arya R, Ravikumar R, Santhosh RS et al. SarA based novel therapeutic candidate against Staphylococcus aureus associated with vascular graft infections. Front Microbiol 2015;6:416
4. Balasubramanian D, Ohneck EA, Chapman J et al. Staphylococcus aureus coordinates leukocidin expression and pathogenesis by sensing metabolic fluxes via RpiRc. MBio 2016;7:e00818-00816
5. Beasley FC, Vines ED, Grigg JC et al. Characterization of staphyloferrin A biosynthetic and transport mutants in Staphylococcus aureus. Mol Microbiol 2009;72:947-63
6. Benson MA, Lilo S, Nygaard T et al. Rot and SaeRS cooperate to activate expression of the staphylococcal superantigen-like exoproteins. J Bacteriol 2012;194:4355-65
7. Benson MA, Lilo S, Wasserman GA et al. Staphylococcus aureus regulates the expression and production of the staphylococcal superantigen-like secreted proteins in a Rot-dependent manner. Mol Microbiol 2011;81:659-75
8. Bocchini CE, Hulten KG, Mason EO, Jr et al. Panton-Valentine leukocidin genes are associated with enhanced inflammatory response and local disease in acute hematogenous Staphylococcus aureus osteomyelitis in children. Pediatrics 2006;117:433-40
9. Boles BR, Horswill AR. Agr-mediated dispersal of Staphylococcus aureus biofilms. PLoS Pathog 2008;4:e1000052
10. Brezis M, Rosen S. Hypoxia of the renal medulla-its implications for disease. N Engl J Med 1995;332:647-55
11. Broker BM, Holtfreter S, Bekeredjian-Ding I. Immune control of Staphylococcus aureus-regulation and counterregulation of the adaptive immune response. Int J Med Microbiol 2014;304:204-14
12. Brooks AJ, Eastwood J, Beckingham IJ et al. Liver tissue partial pressure of oxygen and carbon dioxide during partial hepatectomy. Brit J Anaesth 2004;92:735-7
13. Brooks JL, Jefferson KK. Staphylococcal biofilms: quest for the magic bullet. Adv Appl Microbiol 2012;81:63-87
14. Bullen JJ, Rogers HJ, Griffiths E. Role of iron in bacterial infection. Curr Top Microbiol Immunol 1978;80:1-35
15. Burke KA, Lascelles J. Nitrate reductase system in Staphylococcus aureus wild type andmutants. J Bacteriol 1975;123:308-16
16. Carreau A, El Hafny-Rahbi B, Matejuk A et al. Why is the partial oxygen pressure of human tissues a crucial parameter? Smallmolecules and hypoxia. J Cell Mol Med 2011;15:1239-53
17. Cartwright GE, Lauritsen MA, Humphreys S et al. The anemia associated with chronic infection. Science 1946;103:72-3
18. Cassat JE, Skaar EP. Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity. Semin Immunopathol 2012;34:215-35
19. Cassat JE, Skaar EP. Iron in infection and immunity. Cell Host Microbe 2013;13:509-19
20. Chan PF, Foster SJ. Role of SarA in virulence determinant production and environmental signal transduction in Staphylococcus aureus. J Bacteriol 1998;180:6232-41
21. Cheng AG, Kim HK, Burts ML et al. Genetic requirements for Staphylococcus aureus abscess formation and persistence in host tissues. FASEB J 2009;23:3393-404
22. Cheung AL, Ying P. Regulation of alpha-and beta-hemolysins by the sar locus of Staphylococcus aureus. J Bacteriol 1994;176:580-5
23. Cheung AL, Eberhardt K, Heinrichs JH. Regulation of protein A synthesis by the sar and agr loci of Staphylococcus aureus. Infect Immun 1997;65:2243-9
24. Cheung AL, Koomey JM, Butler CA et al. Regulation of exoprotein expression in Staphylococcus aureus by a locus (sar) distinct from agr. P Natl Acad Sci USA 1992;89:6462-6
25. Cheung AL, Zhang G. Global regulation of virulence determinants in Staphylococcus aureus by the SarA protein family. Front Biosci 2002;7:d1825-42
26. Cheung J, Beasley FC, Liu S et al. Molecular characterization of staphyloferrin B biosynthesis in Staphylococcus aureus. Mol Microbiol 2009;74:594-608
27. Chien Y, Manna AC, Projan SJ et al. SarA, a global regulator of virulence determinants in Staphylococcus aureus, binds to a conservedmotif essential for sar-dependent gene regulation. J Biol Chem 1999;274:37169-76
28. Chien Y, Cheung AL. Molecular interactions between two global regulators, sar and agr, in Staphylococcus aureus. J Biol Chem 1998;273:2645-52
29. Cho H, Jeong DW, Liu Q et al. Calprotectin increases the activity of the SaeRS two component system and murine mortality during Staphylococcus aureus infections. PLoS Pathog 2015;11:e1005026
30. Clements MO, Foster SJ. Starvation recovery of Staphylococcus aureus 8325-4. Microbiology 1998;144 (Pt 7):1755-63
31. Colgan SP, Taylor CT. Hypoxia: an alarm signal during intestinal inflammation. Nat Rev Gastroentero 2010;7:281-7
32. Cramton SE, Ulrich M, Gotz F et al. Anaerobic conditions induce expression of polysaccharide intercellular adhesin in Staphylococcus aureus and Staphylococcus epidermidis. Infect Immun 2001;69:4079-85
33. Daddaoua A, Krell T, Ramos JL. Regulation of glucose metabolism in Pseudomonas: the phosphorylative branch and entner-doudoroff enzymes are regulated by a repressor containing a sugar isomerase domain. J Biol Chem 2009;284:21360-8
34. Dahl A, Hansen TF, Bruun NE. Staphylococcus aureus endocarditis with fast development of aortic root abscess despite relevant antibiotics. Heart Lung 2013;42:72-3
35. Dale SE, Doherty-Kirby A, Lajoie G et al. Role of siderophore biosynthesis in virulence of Staphylococcus aureus: identification and characterization of genes involved in production of a siderophore. Infect Immun 2004;72:29-37
36. Darton TC, Blohmke CJ, Giannoulatou E et al. Rapidly escalating hepcidin and associated serum iron starvation are features of the acute response to typhoid infection in humans. PLoS Neglect Trop D 2015;9:e0004029
37. Date SV,Modrusan Z, LawrenceMet al. Global gene expression of methicillin-resistant Staphylococcus aureus USA300 during human and mouse infection. J Infect Dis 2014;209:1542-50
38. Deiss A. Iron metabolism in reticuloendothelial cells. Semin Hematol 1983;20:81-90
39. den Hengst CD, van Hijum SA, Geurts JM et al. The Lactococcus lactis CodY regulon: identification of a conserved cisregulatory element. J Biol Chem 2005;280:34332-42
40. Deutscher J, Saier MH Jr. ATP-dependent protein kinasecatalyzed phosphorylation of a seryl residue in HPr, a phosphate carrier protein of the phosphotransferase system in Streptococcus pyogenes. P Natl Acad Sci USA 1983;80:6790-4
41. Deutscher J, Kuster E, Bergstedt U et al. Protein kinase-dependent HPr/CcpA interaction links glycolytic activity to carbon catabolite repression in gram-positive bacteria. Mol Microbiol 1995;15:1049-53
42. Ding Y, Liu X, Chen F et al. Metabolic sensor governing bacterial virulence in Staphylococcus aureus. P Natl Acad Sci USA 2014;111:E4981-90
43. Dunyach-Remy C, Ngba Essebe C, Sotto A et al. Staphylococcus aureus toxins and diabetic foot ulcers: role in pathogenesis and interest in diagnosis. Toxins 2016;8:S1262-3636
44. Equils O, da Costa C,WibleMet al. The effect of diabetes mellitus on outcomes of patients with nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus: data from a prospective double-blind clinical trial comparing treatment with linezolid versus vancomycin. BMC Infect Dis 2016;16: 476
45. Fedtke I, Kamps A, Krismer B et al. The nitrate reductase and nitrite reductase operons and the narT gene of Staphylococcus carnosus are positively controlled by the novel twocomponent system NreBC. J Bacteriol 2002;184:6624-34
46. Filice GA, Nyman JA, Lexau C et al. Excess costs and utilization associated with methicillin resistance for patients with Staphylococcus aureus infection. Infect Cont Hosp Ep 2010;31:365-73
47. FillatMF. The FUR (ferric uptake regulator) superfamily: diversity and versatility of key transcriptional regulators. Arch Biochem Biophys 2014;546:41-52
48. Flack CE, Zurek OW, Meishery DD et al. Differential regulation of staphylococcal virulence by the sensor kinase SaeS in response to neutrophil-derived stimuli. P Natl Acad Sci USA 2014;111:E2037-45
49. Foster T. Staphylococcus. In Baron S (ed.). Medical Microbiology. Galveston, TX: University of Texas Medical Branch at Galveston, 1996
50. Fowler VG Jr., Proctor RA. Where does a Staphylococcus aureus vaccine stand? Clin Microbiol Infect 2014;20 Suppl 5:66-75
51. Fowler VG Jr., Sakoulas G, McIntyre LM et al. Persistent bacteremia due to methicillin-resistant Staphylococcus aureus infection is associated with agr dysfunction and low-level in vitro resistance to thrombin-induced platelet microbicidal protein. J Infect Dis 2004;190:1140-9
52. Fuchs S, Pane-Farre J, Kohler C et al. Anaerobic gene expression in Staphylococcus aureus. J Bacteriol 2007;189:4275-89
53. Gabig TG, Bearman SI, Babior BM. Effects of oxygen tension and pH on the respiratory burst of human neutrophils. Blood 1979;53:1133-9
54. Galinier A, Haiech J, Kilhoffer MC et al. The Bacillus subtilis crh gene encodes a HPr-like protein involved in carbon catabolite repression. P Natl Acad Sci USA 1997;94:8439-44
55. Gaupp R, Wirf J, Wonnenberg B et al. RpiRc is a pleiotropic effector of virulence determinant synthesis and attenuates pathogenicity in Staphylococcus aureus. Infect Immun 2016;84:2031-41
56. Geiger T, Goerke C, Mainiero M et al. The virulence regulator Sae of Staphylococcus aureus: promoter activities and response to phagocytosis-related signals. J Bacteriol 2008;190:3419-28
57. Geisinger E, Adhikari RP, Jin R et al. Inhibition of rot translation by RNAIII, a key feature of agr function. Mol Microbiol 2006;61:1038-48
58. Giersing BK, Dastgheyb SS, Modjarrad K et al. Status of vaccine research and development of vaccines for Staphylococcus aureus. Vaccine 2016;34:2962-6
59. Giraudo AT, Raspanti CG, Calzolari A et al. Characterization of a Tn551-mutant of Staphylococcus aureus defective in the production of several exoproteins. Can J Microbiol 1994;40:677-81
60. Giraudo AT, Calzolari A, Cataldi AA et al. The sae locus of Staphylococcus aureus encodes a two-component regulatory system. FEMS Microbiol Lett 1999;177:15-22
61. Gorke B, Stulke J. Carbon catabolite repression in bacteria: many ways to make the most out of nutrients. Nat Rev Microbiol 2008;6:613-24
62. Green J, Paget MS. Bacterial redox sensors. Nat Rev Microbiol 2004;2:954-66
63. Grosser MR, Weiss A, Shaw LN et al. Regulatory requirements for Staphylococcus aureus nitric oxide resistance. J Bacteriol 2016;198:2043-55
64. Guedon E, Serror P, Ehrlich SD et al. Pleiotropic transcriptional repressor CodY senses the intracellular pool of branched-chain amino acids in Lactococcus lactis. Mol Microbiol 2001;40: 1227-39
65. Hall JW, Ji Y. Sensing and Adapting to Anaerobic Conditions by Staphylococcus aureus. Adv Appl Microbiol 2013;84:1-25
66. Hall JW, Yang J, Guo H et al. The AirSR two-component system contributes to Staphylococcus aureus survival in human blood and transcriptionally regulates sspABC operon. Front Microbiol 2015;6:682
67. Hammer ND, Skaar EP. Molecular mechanisms of Staphylococcus aureus iron acquisition. Annu Rev Microbiol 2011;65: 129-47
68. Hantke K. Iron and metal regulation in bacteria. Curr Opin Microbiol 2001;4:172-7
69. Harris LG, Richards RG. Staphylococci and implant surfaces: a review. Injury 2006;37 Suppl 2:S3-14
70. Hartmann T, Zhang B, Baronian G et al. Catabolite control protein E (CcpE) is a LysR-type transcriptional regulator of tricarboxylic acid cycle activity in Staphylococcus aureus. J Biol Chem 2013;288:36116-28
71. Hatzenbuehler J, Pulling TJ. Diagnosis and management of osteomyelitis. Am Fam Physician 2011;84:1027-33
72. Hendrix AS, Spoonmore TJ,Wilde AD et al. Repurposing the nonsteroidal anti-inflammatory drug diflunisal as an osteoprotective, antivirulence therapy for Staphylococcus aureus osteomyelitis. Antimicrob Agents Ch 2016;60:5322-30
73. Henkin TM, Grundy FJ, Nicholson WL et al. Catabolite repression of alpha-amylase gene expression in Bacillus subtilis involves a trans-acting gene product homologous to the Escherichia coli lacl and galR repressors. Mol Microbiol 1991;5:575-84
74. Hogan S, Stevens NT, Humphreys H et al. Current and future approaches to the prevention and treatment of staphylococcal medical device-related infections. Curr Pharm Des 2015;21:100-13
75. Jaeger T, Mayer C. The transcriptional factors MurR and catabolite activator protein regulate N-acetylmuramic acid catabolism in Escherichia coli. J Bacteriol 2008;190: 6598-608
76. Kale P, Dhawan B. The changing face of community-acquired methicillin-resistant Staphylococcus aureus. Indian J Med Microbiol 2016;34:275-85
77. Kamps A, Achebach S, Fedtke I et al. Staphylococcal NreB: an O(2)-sensing histidine protein kinase with an O(2)-labile iron-sulphur cluster of the FNR type. Mol Microbiol 2004;52:713-23
78. Karauzum H, Datta SK. Adaptive immunity against Staphylococcus aureus. Curr Top Microbiol Immunol 2016
79. Khan BA, Yeh AJ, Cheung GY et al. Investigational therapies targeting quorum-sensing for the treatment of Staphylococcus aureus infections. Expert Opin Inv Drug 2015;24:689-704
80. Khodaverdian V, Pesho M, Truitt B et al. Discovery of antivirulence agents against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Ch 2013;57:3645-52
81. Kiedrowski MR, Horswill AR. New approaches for treating staphylococcal biofilm infections. Ann N Y Acad Sci 2011;1241:104-21
82. Killikelly A, Benson MA, Ohneck EA et al. Structure-based functional characterization of repressor of toxin (Rot), a central regulator of Staphylococcus aureus virulence. J Bacteriol 2015;197:188-200
83. Kinkel TL, Roux CM, Dunman PM et al. The Staphylococcus aureus SrrAB two-component system promotes resistance to nitrosative stress and hypoxia. MBio 2013;4:e00696-13
84. Kirchdoerfer RN, Garner AL, Flack CE et al. Structural basis for ligand recognition and discrimination of a quorum-quenching antibody. J Biol Chem 2011;286:17351-8
85. Klevens RM, Morrison MA, Nadle J et al. Invasive methicillinresistant Staphylococcus aureus infections in the United States. JAMA 2007;298:1763-71
86. Kohler PR, Choong EL, Rossbach S. The RpiR-like repressor IolR regulates inositol catabolism in Sinorhizobium meliloti. J Bacteriol 2011;193:5155-63
87. Konetschny-Rapp S, Jung G, Meiwes J et al. Staphyloferrin A: a structurally new siderophore from staphylococci. Eur J Biochem 1990;191:65-74
88. Kuroda H, Kuroda M, Cui L et al. Subinhibitory concentrations of beta-lactam induce haemolytic activity in Staphylococcus aureus through the SaeRS two-component system. FEMS Microbiol Lett 2007;268:98-105
89. Lacey KA, Geoghegan JA, McLoughlin RM. The role of Staphylococcus aureus virulence factors in skin infection and their potential as vaccine antigens. Pathogens 2016;5
90. Leboeuf C, Leblanc L, Auffray Y et al. Characterization of the ccpA gene of Enterococcus faecalis: identification of starvation-inducible proteins regulated by ccpA. J Bacteriol 2000;182:5799-806
91. Levdikov VM, Blagova E, Joseph P et al. The structure of CodY, a GTP-and isoleucine-responsive regulator of stationary phase and virulence in gram-positive bacteria. J Biol Chem 2006;281:11366-73
92. Li D, Cheung A. Repression of hla by rot is dependent on sae in Staphylococcus aureus. Infect Immun 2008;76:1068-75
93. Lister JL, Horswill AR. Staphylococcus aureus biofilms: recent developments in biofilm dispersal. Front Cell Infect Microbiol 2014;4:178
94. Liu M, Tanaka WN, Zhu H et al. Direct hemin transfer from IsdA to IsdC in the iron-regulated surface determinant (Isd) heme acquisition system of Staphylococcus aureus. J Biol Chem 2008;283:6668-76
95. Lone AG, Atci E, Renslow R et al. Staphylococcus aureus induces hypoxia and cellular damage in porcine dermal explants. Infect Immun 2015;83:2531-41
96. Long DR, Mead J, Hendricks JM et al. 18beta-Glycyrrhetinic acid inhibits methicillin-resistant Staphylococcus aureus survival and attenuates virulence gene expression. Antimicrob Agents Ch 2013;57:241-7
97. Loomis WP, Johnson ML, Brasfield A et al. Temporal and anatomical host resistance to chronic Salmonella infection is quantitatively dictated by Nramp1 and influenced by host genetic background. PLoS One 2014;9:e111763
98. Lyon GJ, Novick RP. Peptide signaling in Staphylococcus aureus and other Gram-positive bacteria. Peptides 2004;25:1389-403
99. MacKenzie EL, Iwasaki K, Tsuji Y. Intracellular iron transport and storage: from molecular mechanisms to health implications. Antioxid Redox Sign 2008;10:997-1030
100. Mader JT, Brown GL, Guckian JC et al. A mechanism for the amelioration by hyperbaric oxygen of experimental staphylococcal osteomyelitis in rabbits. J Infect Dis 1980;142:915-22
101. Majerczyk CD, Sadykov MR, Luong TT et al. Staphylococcus aureus CodY negatively regulates virulence gene expression. J Bacteriol 2008;190:2257-65
102. Majerczyk CD, Dunman PM, Luong TT et al. Direct targets of CodY in Staphylococcus aureus. J Bacteriol 2010;192:2861-77
103. Malani PN. National burden of invasive methicillin-resistant Staphylococcus aureus infection. JAMA 2014;311:1438-9
104. Martin-Verstraete I, Deutscher J, Galinier, A. Phosphorylation of HPr and Crh by HprK, early steps in the catabolite repression signalling pathway for the Bacillus subtilis levanase operon. J Bacteriol 1999;181:2966-9
105. Masse E, Gottesman S. A small RNA regulates the expression of genes involved in iron metabolism in Escherichia coli. P Natl Acad Sci USA 2002;99:4620-5
106. Mazmanian SK, Skaar EP, Gaspar AH et al. Passage of hemeiron across the envelope of Staphylococcus aureus. Science 2003;299:906-9
107. Missiakas D, Schneewind O. Staphylococcus aureus vaccines: deviating from the carol. J Exp Med 2016;213:1645-53
108. Miwa Y, Nakata A, Ogiwara A et al. Evaluation and characterization of catabolite-responsive elements (cre) of Bacillus subtilis. Nucleic Acids Res 2000;28:1206-10
109. Monod J. Recherches sur la croissance des cultures bacteriennes (Research on the growth of bacterial cultures). Actua Sci Ind 1942;911:1-215
110. Montgomery CP, Boyle-Vavra S, Daum RS. Importance of the global regulators Agr and SaeRS in the pathogenesis of CAMRSA USA300 infection. PLoS One 2010;5:e15177
111. Montgomery CP, David MZ, Daum RS. Host factors that contribute to recurrent staphylococcal skin infection. Curr Opin Infect Dis 2015;28:253-8
112. Mootz JM, Benson MA, Heim CE et al. Rot is a key regulator of Staphylococcus aureus biofilm formation. Mol Microbiol 2015;96:388-404
113. Morfeldt E, Tegmark K, Arvidson S. Transcriptional control of the agr-dependent virulence gene regulator, RNAIII, in Staphylococcus aureus. Mol Microbiol 1996;21:1227-37
114. Muryoi N, Tiedemann MT, Pluym M et al. Demonstration of the iron-regulated surface determinant (Isd) heme transfer pathway in Staphylococcus aureus. J Biol Chem 2008;283:28125-36
115. Nastaly P, Grinholc M, Bielawski KP. Molecular characteristics of community-associated methicillin-resistant Staphylococcus aureus strains for clinical medicine. Arch Microbiol 2010;192:603-17
116. Nordlie RC, Foster JD, Lange AJ. Regulation of glucose production by the liver. Annu Rev Nutr 1999;19:379-406
117. Novick RP, Jiang D. The staphylococcal saeRS system coordinates environmental signals with agr quorum sensing. Microbiology 2003;149 (Pt 10):2709-17
118. Novick RP, Geisinger E. Quorum sensing in staphylococci. Annu Rev Genet 2008;42:541-64
119. Novick RP, Ross HF, Projan SJ et al. Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule. EMBO J 1993;12:3967-75
120. Nygaard TK, Pallister KB, Ruzevich P et al. SaeR binds a consensus sequence within virulence gene promoters to advance USA300 pathogenesis. J Infect Dis 2010;201:241-54
121. O'Gara JP. ica and beyond: biofilm mechanisms and regulation in Staphylococcus epidermidis and Staphylococcus aureus. FEMS Microbiol Lett 2007;270:179-88
122. Olson ME, Nygaard TK, Ackermann L et al. Staphylococcus aureus nuclease is an SaeRS-dependent virulence factor. Infect Immun 2013;81:1316-24
123. Pagels M, Fuchs S, Pane-Farre J et al. Redox sensing by a Rexfamily repressor is involved in the regulation of anaerobic gene expression in Staphylococcus aureus. Mol Microbiol 2010;76:1142-61
124. Painter KL, Krishna A, Wigneshweraraj S et al. What role does the quorum-sensing accessory gene regulator system play during Staphylococcus aureus bacteremia? Trends Microbiol 2014;22:676-85
125. Park J, Jagasia R, Kaufmann GF et al. Infection control by antibody disruption of bacterial quorum sensing signaling. Chem Biol 2007;14:1119-27
126. Park MK, Myers RA, Marzella L. Oxygen tensions and infections: modulation of microbial growth, activity of antimicrobial agents, and immunologic responses. Clin Infect Dis 1992;14:720-40
127. Park RY, Sun HY, Choi MH et al. Staphylococcus aureus siderophore-mediated iron-acquisition system plays a dominant and essential role in the utilization of transferrin-bound iron. J Microbiol 2005;43:183-90
128. Parsek MR, Singh PK. Bacterial biofilms: an emerging link to disease pathogenesis. Annu Rev Microbiol 2003;57:677-701
129. Pendleton A, Kocher MS. Methicillin-resistant staphylococcus aureus bone and joint infections in children. J Am Acad Orthop Sur 2015;23:29-37
130. Pohl K, Francois P, Stenz L et al. CodY in Staphylococcus aureus: a regulatory link between metabolism and virulence gene expression. J Bacteriol 2009;191:2953-63
131. Pomposelli JJ, Baxter JK, 3rd, Babineau TJ et al. Early postoperative glucose control predicts nosocomial infection rate in diabetic patients. JPEN-Parenter Enter 1998;22:77-81
132. Pragman AA, Yarwood JM, Tripp TJ et al. Characterization of virulence factor regulation by SrrAB, a two-component system in Staphylococcus aureus. J Bacteriol 2004;186:2430-8
133. Psychogios N, Hau DD, Peng J et al. The human serum metabolome. PLoS One 2011;6:e16957
134. Queck SY, Jameson-Lee M, Villaruz AE et al. RNAIII-independent target gene control by the agr quorum-sensing system: insight into the evolution of virulence regulation in Staphylococcus aureus. Mol Cell 2008;32:150-8
135. Ratnayake-Lecamwasam M, Serror P, Wong KW et al. Bacillus subtilis CodY represses early-stationary-phase genes by sensing GTP levels. Genes Dev 2001;15:1093-103
136. Recsei P, Kreiswirth B, O'Reilly M et al. Regulation of exoprotein gene expression in Staphylococcus aureus by agar. Mol Gen Genet 1986;202:58-61
137. Rich J, Lee JC. The pathogenesis of Staphylococcus aureus infection in the diabetic NOD mouse. Diabetes 2005;54:2904-10
138. Richards MJ, Edwards JR, Culver DH et al. Nosocomial infections in medical intensive care units in the United States. National Nosocomial Infections Surveillance System. Crit Care Med 1999;27:887-92
139. Roux A, Todd DA, Velazquez JV et al. CodY-mediated regulation of the Staphylococcus aureus Agr system integrates nutritional and population density signals. J Bacteriol 2014;196: 1184-96
140. Rubinstein E. Staphylococcus aureus bacteraemia with known sources. Int J Antimicrob Ag 2008;32 (Suppl 1):S18-20
141. Sader HS, Mendes RE, Jones RN et al. Antimicrobial susceptibility patterns of community-and hospital-acquired methicillinresistant Staphylococcus aureus from United States Hospitals: results from the AWARE Ceftaroline Surveillance Program (2012-2014). Diagn Microbiol Infect Dis 2016;86:76-9
142. Said-Salim B, Dunman PM, McAleese FM et al. Global regulation of Staphylococcus aureus genes by Rot. J Bacteriol 2003;185:610-9
143. Saier MH Jr., Chauvaux S, Cook GM et al. Catabolite repression and inducer control in Gram-positive bacteria. Microbiology 1996;142 (Pt2):217-30
144. Schaffer K, Taylor CT. The impact of hypoxia on bacterial infection. FEBS J 2015;282:2260-6
145. Scherr TD, Heim CE, Morrison JM et al. Hiding in plain sight: interplay between staphylococcal biofilms and host immunity. Front Immunol 2014;5:37
146. Schlag S, Fuchs S, Nerz C et al. Characterization of the oxygenresponsive NreABC regulon of Staphylococcus aureus. J Bacteriol 2008;190:7847-58
147. Schlievert PM, Merriman JA, Salgado-Pabon W et al. Menaquinone analogs inhibit growth of bacterial pathogens. Antimicrob Agents Ch 2013;57:5432-7
148. Schweizer ML, Furuno JP, Sakoulas G et al. Increased mortality with accessory gene regulator (agr) dysfunction in Staphylococcus aureus among bacteremic patients. Antimicrob Agents Ch 2011;55:1082-7
149. Seidl K, Goerke C, Wolz C et al. Staphylococcus aureus CcpA affects biofilm formation. Infect Immun 2008;76:2044-50
150. Seidl K, Muller S, Francois P et al. Effect of a glucose impulse on the CcpA regulon in Staphylococcus aureus. BMC Microbiol 2009;9:95
151. Seidl K, Stucki M, Ruegg M et al. Staphylococcus aureus CcpA affects virulence determinant production and antibiotic resistance. Antimicrob Agents Ch 2006;50:1183-94
152. Sheen TR, Ebrahimi CM, Hiemstra IH et al. Penetration of the blood-brain barrier by Staphylococcus aureus: contribution of membrane-anchored lipoteichoic acid. J Mol Med (Berl) 2010;88:633-9
153. Shivers RP, Sonenshein AL. Activation of the Bacillus subtilis global regulator CodY by direct interaction with branchedchain amino acids. Mol Microbiol 2004;53:599-611
154. Shopsin B, Drlica-Wagner A, Mathema B et al. Prevalence of agr dysfunction among colonizing Staphylococcus aureus strains. J Infect Dis 2008;198:1171-4
155. Singh R, Ray P. Quorum sensing-mediated regulation of staphylococcal virulence and antibiotic resistance. Future Microbiol 2014;9:669-81
156. Skaar EP, Humayun M, Bae T et al. Iron-source preference of Staphylococcus aureus infections. Science 2004;305:1626-8
157. Skaar EP, Gaspar AH, Schneewind O. IsdG and IsdI, hemedegrading enzymes in the cytoplasm of Staphylococcus aureus. J Biol Chem 2004;279:436-43
158. Somerville GA, Proctor RA. At the crossroads of bacterial metabolism and virulence factor synthesis in Staphylococci. Microbiol Mol Biol R 2009;73:233-48
159. Sonenshein AL. Control of key metabolic intersections in Bacillus subtilis. Nat Rev Microbiol 2007;5:917-27
160. Sorensen KI, Hove-Jensen B. Ribose catabolism of Escherichia coli: characterization of the rpiB gene encoding ribose phosphate isomerase B and of the rpiR gene, which is involved in regulation of rpiB expression. J Bacteriol 1996;178:1003-11
161. Spaan AN, Vrieling M, Wallet P et al. The staphylococcal toxins gamma-haemolysin AB and CB differentially target phagocytes by employing specific chemokine receptors. Nat Commun 2014;5:5438
162. Spaan AN, Reyes-Robles T, Badiou C et al. Staphylococcus aureus targets the duffy antigen receptor for chemokines (DARC) to lyse erythrocytes. Cell Host Microbe 2015;18:363-70
163. Spencer JA, Ferraro F, Roussakis E et al. Direct measurement of local oxygen concentration in the bone marrow of live animals. Nature 2014;508:269-73
164. Sterba KM, Mackintosh SG, Blevins JS et al. Characterization of Staphylococcus aureus SarA binding sites. J Bacteriol 2003;185:4410-7
165. Strasters KC, Winkler KC. Carbohydrate metabolism of Staphylococcus aureus. J Gen Microbiol 1963;33:213-29
166. Suaya JA, Mera RM, Cassidy A et al. Incidence and cost of hospitalizations associated with Staphylococcus aureus skin and soft tissue infections in the United States from 2001 through 2009. BMC Infect Dis 2014;14:296
167. Sully EK, Malachowa N, Elmore BO et al. Selective chemical inhibition of agr quorum sensing in Staphylococcus aureus promotes host defense with minimal impact on resistance. PLoS Pathog 2014;10:e1004174
168. Sun F, Li C, Jeong D et al. In the Staphylococcus aureus twocomponent system sae, the response regulator SaeR binds to a direct repeat sequence and DNA binding requires phosphorylation by the sensor kinase SaeS. J Bacteriol 2010;192: 2111-27
169. Sun F, Liang H, Kong X et al. Quorum-sensing agr mediates bacterial oxidation response via an intramolecular disulfide redox switch in the response regulator AgrA. P Natl Acad Sci USA 2012a;109:9095-100
170. Sun F, Ji Q, Jones MB et al. AirSR, a [2Fe-2S] cluster-containing two-component system, mediates global oxygen sensing and redox signaling in Staphylococcus aureus. J AmChemSoc 2012b;134:305-14
171. Sun J, Zheng L, Landwehr C et al. Identification of a novel essential two-component signal transduction system, YhcSR, in Staphylococcus aureus. J Bacteriol 2005;187:7876-80
172. Tal-Gan Y, Stacy DM, FoegenMK et al. Highly potent inhibitors of quorum sensing in Staphylococcus aureus revealed through a systematic synthetic study of the group-III autoinducing peptide. J Am Chem Soc 2013;135:7869-82
173. Throup JP, Zappacosta F, Lunsford RD et al. The srhSR gene pair from Staphylococcus aureus: genomic and proteomic approaches to the identification and characterization of gene function. Biochemistry 2001;40:10392-401
174. Titgemeyer F, Hillen W. Global control of sugar metabolism: a gram-positive solution. Anton Leeuw 2002;82:59-71
175. Tojo S, Satomura T, Morisaki K et al. Elaborate transcription regulation of the Bacillus subtilis ilv-leu operon involved in the biosynthesis of branched-chain amino acids through global regulators of CcpA, CodY and TnrA. Mol Microbiol 2005;56:1560-73
176. Tong SY, Davis JS, Eichenberger E et al. Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev 2015;28:603-61
177. Torres VJ, Pishchany G, HumayunMet al. Staphylococcus aureus IsdB is a hemoglobin receptor required for heme iron utilization. J Bacteriol 2006;188:8421-9
178. Torres VJ, Attia AS, Mason WJ et al. Staphylococcus aureus fur regulates the expression of virulence factors that contribute to the pathogenesis of pneumonia. Infect Immun 2010;78:1618-28
179. Traber KE, Lee E, Benson S et al. agr function in clinical Staphylococcus aureus isolates. Microbiology 2008;154 (Pt 8):2265-74
180. Tripathi A, Schofield MM, Chlipala GE et al. Baulamycins A and B, broad-spectrum antibiotics identified as inhibitors of siderophore biosynthesis in Staphylococcus aureus and Bacillus anthracis. J Am Chem Soc 2014;136:1579-86
181. Trotonda MP, Manna AC, Cheung AL et al. SarA positively controls bap-dependent biofilm formation in Staphylococcus aureus. J Bacteriol 2005;187:5790-8
182. Troxell B, Hassan HM. Transcriptional regulation by Ferric Uptake Regulator (Fur) in pathogenic bacteria. Front Cell Infect Microbiol 2013;3:59
183. Ulrich M, Bastian M, Cramton SE et al. The staphylococcal respiratory response regulator SrrAB induces ica gene transcription and polysaccharide intercellular adhesin expression, protecting Staphylococcus aureus from neutrophil killing under anaerobic growth conditions. Mol Microbiol 2007;65:1276-87
184. Vitko NP, GrosserMR, Khatri D et al. Expanded glucose import capability affords Staphylococcus aureus optimized glycolytic flux during infection. MBio 2016;7:e00296-00216
185. Vitko NP, Spahich NA, Richardson AR. Glycolytic dependency of high-level nitric oxide resistance and virulence in Staphylococcus aureus. MBio 2015;6:e00045-00015
186. von Eiff C, Becker K, Metze D et al. Intracellular persistence of Staphylococcus aureus small-colony variants within keratinocytes: a cause for antibiotic treatment failure in a patient with darier's disease. Clin Infect Dis 2001;32:1643-7
187. Vuong C, Kocianova S, Voyich JM et al. A crucial role for exopolysaccharide modification in bacterial biofilm formation, immune evasion, and virulence. J Biol Chem 2004;279: 54881-6
188. Waldrop R, McLaren A, Calara F et al. Biofilm growth has a threshold response to glucose in vitro. Clin Orthop Relat R 2014;472:3305-10
189. Wang B, Muir TW. Regulation of virulence in Staphylococcus aureus: molecular mechanisms and remaining puzzles. Cell Chem Biol 2016;23:214-24
190. Warner JB, Lolkema JS. CcpA-dependent carbon catabolite repression in bacteria. Microbiol Mol Biol R 2003;67:475-90
191. Watson SP, Clements MO, Foster SJ. Characterization of the starvation-survival response of Staphylococcus aureus. J Bacteriol 1998;180:1750-8
192. Wertheim HF, Melles DC, Vos MC et al. The role of nasal carriage in Staphylococcus aureus infections. Lancet Infect Dis 2005;5:751-62
193. Wilde AD, Snyder DJ, Putnam NE et al. Bacterial hypoxic responses revealed as critical determinants of the hostpathogen outcome by TnSeq analysis of Staphylococcus aureus invasive infection. PLoS Pathog 2015;11:e1005341
194. Xiong A, Singh VK, Cabrera G et al. Molecular characterization of the ferric-uptake regulator, fur, fromStaphylococcus aureus. Microbiology 2000;146 (Pt 3):659-68
195. Xue T, You Y, Shang F et al. Rot and Agr system modulate fibrinogen-binding ability mainly by regulating clfB expression in Staphylococcus aureus NCTC8325. Med Microbiol Immun 2012;201:81-92
196. Yan M, Yu C, Yang J et al. The essential two-component system YhcSR is involved in regulation of the nitrate respiratory pathway of Staphylococcus aureus. J Bacteriol 2011;193:1799-805
197. Yan M, Hall JW, Yang J et al. The essential yhcSR two-component signal transduction system directly regulates the lac and opuCABCD operons of Staphylococcus aureus. PLoS One 2012;7:e50608
198. Yarwood JM, McCormick JK, Schlievert PM. Identification of a novel two-component regulatory system that acts in global regulation of virulence factors of Staphylococcus aureus. J Bacteriol 2001;183:1113-23
199. Zeitouni NE, Chotikatum S, von Kockritz-Blickwede M et al. The impact of hypoxia on intestinal epithelial cell functions: consequences for invasion by bacterial pathogens. Mol Cell Pediatr 2016;3:14
200. Zhu Y, Nandakumar R, Sadykov MR et al. RpiR homologues may link Staphylococcus aureus RNAIII synthesis and pentose phosphate pathway regulation. J Bacteriol 2011;193:6187-96