Production of β-lactamase inhibitors by Streptomyces species

Antibiotics

Volumn 7, Issue 3, 2018, Pages

  Viana Marques, Daniela de Araújo ^a   Machado, Suellen Emilliany Feitosa ^b   Carvalho Santos Ebinuma, Valéria ^c   Duarte, Carolina de Albuquerque Lima ^a   Converti, Attilio ^d   Porto, Ana Lúcia Figueiredo ^e  

^a FEDERAL UNIVERSITY OF PERNAMBUCO   (Brazil)

^b FEDERAL UNIVERSITY OF PERNAMBUCO   (Brazil)

^c SÃO PAULO STATE UNIVERSITY UNESP   (Brazil)

^d UNIVERSITY OF GENOA   (Italy)

^e UNIVERSIDADE FEDERAL RURAL DE PERNAMBUCO   (Brazil)

Author keywords

Actinobacteria; Antibiotic; Resistance; lactamase; lactamase inhibitor

Indexed keywords

AAI 101; AMINO ACID; AZTREONAM; BENZATHINE PENICILLIN; BETA LACTAMASE; BETA LACTAMASE INHIBITOR; BIAPENEM; CARBENICILLIN; CEFEPIME; CEFPIROME; CEFTAZIDIME; CEFTRIAXONE; CEPHALOSPORIN DERIVATIVE; CEPHAMYCIN DERIVATIVE; CLAVULANIC ACID; CLOXACILLIN; NITROGEN; OXACILLIN; PENICILLIN G; RELEBACTAM; SULBACTAM; TAZOBACTAM; VABORBACTAM;

ACINETOBACTER BAUMANNII; ANAEROBIC FERMENTATION; ANTIBIOTIC RESISTANCE; BACTERIAL STRAIN; CARBON SOURCE; CLINICAL PRACTICE; DNA SEQUENCE; ENTEROBACTER; ESCHERICHIA COLI; GENETIC ENGINEERING; HAEMOPHILUS INFLUENZAE; HELICOBACTER PYLORI; KLEBSIELLA PNEUMONIAE; METABOLIC ENGINEERING; MINIMUM INHIBITORY CONCENTRATION; MYCOBACTERIUM TUBERCULOSIS; NEISSERIA GONORRHOEAE; NONHUMAN; PH; PRIORITY JOURNAL; PROTEUS; PROVIDENCIA; PSEUDOMONAS AERUGINOSA; PURIFICATION; REVIEW; SALMONELLA; SERRATIA; SHIGELLA; STAPHYLOCOCCUS AUREUS; STREPTOCOCCUS PNEUMONIAE; STREPTOMYCES; TRANSGENIC MICROORGANISM;

EID: 85050563386     PISSN: None     EISSN: 20796382     Source Type: Journal    
DOI: 10.3390/antibiotics7030061     Document Type: Review

References (179)

1. Procópio, R.E.; Silva, I.R.; Martins, M.K.; Azevedo, J.L.; Araújo, J.M. Antibiotics produced by Streptomyces. Braz. J. Infect. Dis. 2012, 16, 466–471. [CrossRef] [PubMed]
2. Radlinski, L.; Conlon, B.P. Antibiotic efficacy in the complex infection environment. Curr. Opin. Microbiol. 2018, 42, 19–24. [CrossRef] [PubMed]
3. 1.5: Cultural effect. Rev. Microbiol. 1998, 29, 254–257. [CrossRef]
4. Mohanraj, G.; Sekar, T. Isolation and screening of actinomycetes from marine sediments for their potential to produce antimicrobials. Int. J. Life Sci. Pharm. Res. 2013, 2, 115–126.
5. Kirk, S.; Avogmpme-Rossa, C.A.; Bushell, M.E. Growth limiting substrate affects antibiotic production and associated metabolic flues in Streptomyces clavuligerus. Biotechnol. Lett. 2000, 22, 1803–1809. [CrossRef]
6. Gouveia, E.R.; Baptista-Neto, A.; Badino, A.C., Jr.; Hokka, C.O. Optimisation of medium composition for clavulanic acid production by Streptomyces clavuligerus. Biotechnol. Lett. 2001, 23, 157–161. [CrossRef]
7. Ortiz, S.C.A.; Hokka, C.O.; Badino, A.C., Jr. Utilization of soybean derivatives on clavulanic acid production by Streptomyces clavuligerus. Enzyme Microb. Technol. 2007, 40, 1071–1077. [CrossRef]
8. Ehrlich, J.; Bartz, Q.R.; Smith, R.M.; Joslyn, D.A.; Burkholder, P.R. Chloromycetin, a new antibiotic from a soil actinomycete. Science 1947, 106, 417. [CrossRef] [PubMed]
9. Sethi, S.; Kumar, R.; Gupta, S. Antibiotic production by microbes isolated from soil. Int. J. Pharm. Sci. Res. 2013, 4, 2967–2973. [CrossRef]
10. Drawz, S.M.; Bonomo, R.A. Three Decades of β-Lactamase Inhibitors. Clin. Microbiol. Rev. 2010, 23, 160–201. [CrossRef] [PubMed]
11. Bush, K.; Bradford, P.A. β-Lactams and β-Lactamase Inhibitors: An Overview. Cold Spring Harbor Perspect. Med. 2016, 6, 1–22. [CrossRef] [PubMed]
12. Bradford, P.A. Extended-spectrum β-lactamases in the 21st century: Characterization, epidemiology, and detection of this important resistance threat. Clin. Microbiol. Rev. 2001, 14, 933–951. [CrossRef] [PubMed]
13. Simpson, I.N.; Harper, P.B.; O’Callaghan, C.H. Principal beta–lactamases responsible for resistance to beta-lactam antibiotics in urinary tract infections. Antimicrob. Agents Chemother. 1980, 17, 929–936. [CrossRef] [PubMed]
14. Borodina, I.; Siebring, J.; Zhang, J.; Smith, C.P.; van Keulen, G.; Dijkhuizen, L.; Nielsen, J. Antibiotic Overproduction in Streptomyces coelicolor A3(2) Mediated by Phosphofructokinase Deletion. J. Biol. Chem. 2008, 283, 25186–25199. [CrossRef] [PubMed]
15. Watve, M.G.; Tickoo, R.; Jog, M.M.; Bhole, B.D. How many antibiotics are produced by the genus Streptomyces? Arch. Microbiol. 2001, 176, 386–390. [CrossRef] [PubMed]
16. Abraham, E.P.; Chain, E. An enzyme from bacteria able to destroy penicillin. Rev. Infect. Dis. 1988, 10, 677–678. [CrossRef] [PubMed]
17. Plough, H.H. Penicillin resistance of Staphylococcus aureus and its clinical implications. Am. J. Clin. Pathol. 1945, 15, 446–451. [CrossRef] [PubMed]
18. Bondi, A., Jr.; Dietz, C.C. Penicillin resistant staphylococci. Proc. Soc. Exp. Biol. Med. 1945, 60, 55–58. [CrossRef] [PubMed]
19. Eriksen, K.R. Studies on induced resistance to penicillin in pneumococcus type I. Acta Pathol. Microbiol. Scand. 1945, 22, 398–405. [CrossRef] [PubMed]
20. Gots, J.S. Production of extracellular penicillin-inactivating substances associated with penicillin resistance in Staphylococcus aureus. Proc. Soc. Exp. Biol. Med. 1945, 60, 165–168. [CrossRef] [PubMed]
21. Miller, C.P.; Bohnhoff, M. Studies on the action of penicillin; development of penicillin resistance by gonococcus. Proc. Soc. Exp. Biol. Med. 1945, 60, 354–356. [CrossRef] [PubMed]
22. Waksman, S.A.; Reilly, H.C.; Schatz, A. Strain specificity and production of antibiotic substances: V. Strain resistance of bacteria to antibiotic substances, especially streptomycin. Proc. Natl. Acad. Sci. USA 1945, 31, 157–164. [CrossRef] [PubMed]
23. Hassan, A.; Usman, J.; Kaleem, F.; Omair, M.; Khalid, A.; Iqbal, M. Evaluation of different detection methods of biofilm formation in the clinical isolates. Braz. J. Infect. Dis. 2011, 15, 305–311. [CrossRef]
24. Allen, H.K.; Donato, J.; Wang, H.H.; Cloud-Hansen, K.A.; Davies, J.; Handelsman, J. Call of the wild: Antibiotic resistance genes in natural environments. Nat. Rev. Microbiol. 2010, 8, 251–259. [CrossRef] [PubMed]
25. Petchiappan, A.; Chatterji, D. Antibiotic Resistance: Current Perspectives. ACS Omega 2017, 2, 7400–7409. [CrossRef]
26. Andersson, D.I.; Hughes, D. Microbiological effects of sublethal levels of antibiotics. Nat. Rev. Microbiol. 2014, 12, 465–478. [CrossRef] [PubMed]
27. Hiltunen, T.; Virta, M.; Laine, A.L. Antibiotic resistance in the wild: An eco-evolutionary perspective. Philos. Trans. R. Soc. B Biol. Sci. 2017, 19, 1–7. [CrossRef] [PubMed]
28. World Health Organization. Antibacterial Agents in Clinical Development: An Analysis of the Antibacterial Clinical Development Pipeline, Including Tuberculosis; WHO: Geneva, Switzerland, 2017.
29. Brown, E.D.; Wright, G.D. Antibacterial drug discovery in the resistance era. Nature 2016, 529, 336–343. [CrossRef] [PubMed]
30. Bignell, D.R.D.; Seipke, R.F.; Huguet-Tapia, J.C.; Chambers, A.H.; Parry, R.J.; Loria, R. Streptomyces scabies 87-22 contains a coronafacic acid-like biosynthetic cluster that contributes to plant–microbe interactions. Mol. Plant-Microbe Interact. 2010, 23, 161–175. [CrossRef] [PubMed]
31. Fernandes, P. Antibacterial discovery and development—The failure of success? Nat. Biotechnol. 2006, 24, 1497–1503. [CrossRef] [PubMed]
32. Fischbach, M.A.; Walsh, C.T. Antibiotics for emerging pathogens. Science 2009, 325, 1089–1093. [CrossRef] [PubMed]
33. Ogawara, H. Self-resistance in Streptomyces, with Special Reference to β-Lactam Antibiotics. Molecules 2016, 21, 605. [CrossRef] [PubMed]
34. Docquier, J.D.; Mangani, S. An update on β-lactamase inhibitor discovery and development. Drug Resist. Updat. 2018, 36, 13–29. [CrossRef] [PubMed]
35. Coulthurst, S.J.; Barnard, A.M.L.; Salmond, G.P.C. Regulation and biosynthesis of carbapenem antibiotics in bacteria. Nat. Rev. Microbiol. 2005, 3, 295–306. [CrossRef] [PubMed]
36. Santos, V.C.; Pereira, J.F.B.; Haga, R.B.; Rangel-Yagui, C.O.; Teixeira, J.A.C.; Converti, A.; Pessoa, A., Jr. Stability of clavulanic acid under variable pH, ionic strength and temperature conditions. A new kinetic approach. Biochem. Eng. J. 2009, 45, 89–93. [CrossRef]
37. Zeng, X.; Lin, J. Beta-lactamase induction and cell wall metabolism in Gram-negative bacteria. Front. Microbiol. 2013, 4, 128. [CrossRef] [PubMed]
38. Cohen, M.L. Changing patterns of infectious disease. Nature 2000, 406, 762–767. [CrossRef] [PubMed]
39. Munita, J.M.; Arias, C.A. Mechanisms of antibiotic resistance. Microbiol. Spectr. 2016, 4, 1–37.
40. Wang, W.-J.; Wang, Q.; Zhang, Y.; Lu, R.; Zhang, Y.-L.; Yang, K.-W.; Lei, J.E. Characterization of β-lactamase activity using isothermal titration calorimetry. Biochim. Biophys. Acta 2017, 1861, 2031–2038. [CrossRef] [PubMed]
41. Bush, K. A resurgence of β-lactamase inhibitor combinations effective against multidrug-resistant Gram-negative pathogens. Int. J. Antimicrob. 2015, 46, 483–493. [CrossRef] [PubMed]
42. Papp-Wallace, K.M.; Bonomo, R.A. New β-Lactamase inhibitors in the clinic. Infect. Dis. Clin. N. Am. 2016, 30, 441–464. [CrossRef] [PubMed]
43. Bush, K.; Jacoby, G.A.; Medeiros, A. Functional classification scheme for β-lactamases and its correlation with molecular structure. Antimicrob. Agents Chemother. 1995, 39, 1211–1233. [CrossRef] [PubMed]
44. Bush, K.; Jacoby, G.A. Updated functional classification of beta-lactamases. Antimicrob. Agents Chemother. 2010, 54, 969–976. [CrossRef] [PubMed]
45. Laxminarayan, R.; Matsoso, P.; Pant, S.; Brower, C.; Røttingen, J.-A.; Klugman, K.; Davies, S. Access to effective antimicrobials: A worldwide challenge. Lancet 2016, 387, 168–175. [CrossRef]
46. Bush, K. β-Lactamase inhibitors from laboratory to clinic. Clin. Microbiol. Rev. 1988, 1, 109–123. [CrossRef] [PubMed]
47. Silva, M.S.C.; de Carvaiho Santos-Ebinuma, V.; Lopes, A.M.; de Oliveira Rangel-Yagui, C. Dextran sulfate/Triton X two-phase micellar systems as an alternative first purification step for clavulanic acid. Fluid Phase Equilib. 2015, 399, 80–86. [CrossRef]
48. Akova, M. Sulbactam-containing b-lactamase inhibitor combinations. Clin. Microbiol. Infect. 2008, 14, 185–188. [CrossRef] [PubMed]
49. Jacqueline, C.; Howland, K.; Chesnel, L. In vitro activity of ceftolozane/tazobactam in combination with other classes of antibacterial agents. J. Glob. Antimicrob. Resist. 2017, 10, 326–329. [CrossRef] [PubMed]
50. Balci, C.; Uzun, O.; Arici, M.; Hayran, S.A.; Yuce, D.; Unal, S. Nephrotoxicity of piperacillin-tazobactam combined with vancomycin: Should it be a concern? Int. J. Antimicrob. Agents 2018, in press. [CrossRef] [PubMed]
51. Fast, W.; Sutton, L.D. Metallo-β-lactamase: Inhibitors and reporter substrates. Biochim. Biophys. Acta 2013, 1834, 1648–1659. [CrossRef] [PubMed]
52. Ball, M.; Boyd, A.; Ensor, G.J.; Evans, M.; Golden, M.; Linke, S.R.; Milne, D.; Murphy, R.; Telford, A.; Kalyan, Y.; et al. Development of a manufacturing route to avibactam, a β-lactamase inhibitor. Org. Process Res. Dev. 2016, 20, 1799–1805. [CrossRef]
53. Ohnishi, Y.; Ishikawa, J.; Hara, H.; Suzuki, H.; Ikenoya, M.; Ikeda, H.; Yamashita, A.; Hattori, M.; Horinouchi, S. Genome sequence of the streptomycin-producing microorganism Streptomyces griséus IFO 13350. J. Bacteriol. 2008, 190, 4050–4060. [CrossRef] [PubMed]
54. Drawz, S.M.; Papp-Wallace, K.M.; Bonomo, R.A. New β-lactamase inhibitors: A therapeutic renaissance in an MDR world. Antimicrob. Agents Chemother. 2014, 58, 1835–1846. [CrossRef] [PubMed]
55. Grigorenko, V.G.; Andreeva, I.P.; Rubtsova, M.Y.; Deygen, I.M.; Antipin, R.L.; Majouga, A.G.; Egorov, A.M.; Beshnova, D.A.; Kallio, J.; Hackenberg, C.; et al. Novel non-β-lactam inhibitor of b-lactamase TEM-171 based on acylated phenoxyaniline. Biochimie 2017, 132, 45–53. [CrossRef] [PubMed]
56. Thomson, J.M.; Distler, A.M.; Bonomo, R.A. Overcoming resistance to β-lactamase inhibitors: Comparing Sulbactam to novel inhibitors against clavulanate resistant SHV enzymes with substitutions at Ambler position 244. Biochemistry 2007, 46, 11361–11368. [CrossRef] [PubMed]
57. Saudagar, P.S.; Survase, S.A.; Singhal, R.S. Clavulanic acid: A review. Biotechnol. Adv. 2008, 26, 335–351. [CrossRef] [PubMed]
58. McGowan, S.J.; Bycroft, B.W.; Salmond, G.P.C. Bacterial production of carbapenems and clavams: Evolution of β-lactam antibiotic pathways. Trends Microbiol. 1998, 6, 203–208. [CrossRef]
59. Özcengiz, G.; Demain, A.L. Recent advances in the biosynthesis of penicillins, cephalosporins and clavams and its regulation. Biotechnol. Adv. 2013, 31, 287–311. [CrossRef] [PubMed]
60. Hamed, R.B.; Gomez-Castellanos, J.R.; Henry, L.; Ducho, C.; McDonough, M.A.; Schofield, C.J. The enzymes of β-lactam biosynthesis. Nat. Prod. Rep. 2013, 30, 21–107. [CrossRef] [PubMed]
61. Nobary, S.G.; Jensen, S.E. A comparison of the clavam biosynthetic gene clusters in Streptomyces antibioticus Tü1718 and Streptomyces clavuligerus. Can. J. Microbiol. 2012, 58, 413–425. [CrossRef] [PubMed]
62. Song, J.Y.; Jensen, S.L.; Lee, K.J. Clavulanic acid biosynthesis and genetic manipulation for its overproduction. Appl. Microbiol. Biotechnol. 2010, 88, 659–669. [CrossRef] [PubMed]
63. Ramirez-Malule, H.; Restrepo, A.; Cardona, W.; Junne, S.; Neubauer, P.; Rios-Estepa, R. Inversion of the stereochemical configuration (3S,5S)-clavaminic acid into (3R,5R)-clavulanic acid: A computationally-assisted approach based on experimental evidence. J. Theor. Biol. 2016, 395, 40–50. [CrossRef] [PubMed]
64. Qin, R.; Zhong, C.; Zong, G.; Fua, J.; Pang, X.; Cao, G. Improvement of clavulanic acid production in Streptomyces clavuligerus F613-1 by using a claR-neo reporter strategy. Electron. J. Biotechnol. 2017, 28, 41–46. [CrossRef]
65. Ünsaldı, E.; Kurt-Kızıldogan, A.; Voigt, B.; Becher, D.; Ozcengiz, G. Proteome-wide alterations in an industrial clavulanic acid producing strain of Streptomyces clavuligerus. Synth. Syst. Biotechnol. 2017, 2, 39–48. [CrossRef] [PubMed]
66. Tahlan, K.; Anders, C.; Wong, A.; Mosher, R.H.; Beatty, P.H.; Brumlik, M.J.; Griffin, A.; Hughes, C.; Griffin, J.; Barton, B.; et al. 5S clavam biosynthetic genes are located in both the clavam and paralog gene clusters in Streptomyces clavuligerus. Chem. Biol. 2007, 14, 131–142. [CrossRef] [PubMed]
67. Costa, C.L.L.; Badino, A.C. Overproduction of clavulanic acid by extractive fermentation. Electron. J. Biotechnol. 2015, 18, 154–160. [CrossRef]
68. Haga, R.B.; Santos-Ebinuma, V.C.; Silva, M.S.C.; Pessoa, A., Jr.; Rangel-Yagui, C.O. Clavulanic acid partitioning in charged aqueous two-phase micellar systems. Sep. Purif. Technol. 2013, 273–278. [CrossRef]
69. Viana-Marques, D.A.; Santos-Ebinuma, V.C.; Pessoa, A., Jr.; Porto, A.L.; Torres, B.R.; Converti, A. Effect of aeration and agitation on extractive fermentation of clavulanic acid by using aqueous two-phase system. Biotechnol. Prog. 2016, 32, 1444–1452. [CrossRef] [PubMed]
70. Rodrigues, K.C.S.; Souza, A.T.; Badino, A.C.; Pedrolli, D.B.; Cerri, M.O. Screening of medium constituents for clavulanic acid production by Streptomyces clavuligerus. Braz. J. Microbiol 2018, in press. [CrossRef] [PubMed]
71. Forte, M.B.S.; Taviot-Guého, C.; Leroux, F.; Rodrigues, M.I.; Maugeri Filho, F. Clavulanic acid separation on fixed bed columns of layered double hydroxides: Optimization of operating parameters using breakthrough curves. Process Biochem. 2016, 51, 509–516. [CrossRef]
72. Kumar, P.S.; Duraipandiyan, V.; Ignacimuthu, S. Isolation, screening and partial purification of antimicrobial antibiotics from soil Streptomyces sp. SCA 7. Kaohsiung J. Med. Sci. 2014, 30, 435–446. [CrossRef] [PubMed]
73. Charusanti, P.; Fong, N.L.; Nagarajan, H.; Pereira, A.R.; Li, H.J.; Abate, E.A.; Su, Y.; Gerwick, W.H.; Palsson, B.O. Exploiting adaptive laboratory evolution of streptomyces clavuligerus for antibiotic discovery and overproduction. PLoS ONE 2012, 7, e033727. [CrossRef] [PubMed]
74. Singh, V.; Haque, S.; Singh, H.; Verma, J.; Vibha, K.; Singh, R.; Jawed, A.; Tripathi, C.K.M. Isolation, screening, and identification of novel isolates of Actinomycetes from India for antimicrobial applications. Front. Microbiol. 2016, 7, 1921. [CrossRef] [PubMed]
75. Chater, K.F. Recent advances in understanding Streptomyces. F1000Research 2016, 5, 2795. [CrossRef] [PubMed]
76. Al husnan, L.A.; Alkahtani, M.D.F. Molecular Identification of Streptomyces producing antibiotics and their antimicrobial activities. Ann. Agric. Sci. 2016, 61, 251–255. [CrossRef]
77. Weber, T.; Charusanti, P.; Musiol-Kroll, E.M.; Jiang, X.; Tong, Y.; Kim, H.U.; Lee, S.Y. Metabolic engineering of antibiotic factories: New tools for antibiotic production in actinomycetes. Trends Biotechnol. 2015, 33, 15–26. [CrossRef] [PubMed]
78. Balachandran, C.; Duraipandiyan, V.; Arund, Y.; Sangeetha, B.; Emi, N.; Al-Dhabi, N.A.; Ignacimuthu, S.; Inaguma, Y.; Okamoto, A.; Perumal, P.T. Isolation and characterization of 2-hydroxy-9,10-anthraquinone from Streptomyces olivochromogenes (ERINLG-261) with antimicrobial and antiproliferative properties. Rev. Bras. Farmacogn. 2016, 26, 285–295. [CrossRef]
79. Martínez-Burgo, Y.; Álvarez-Álvarez, R.; Pérez-Redondo, R.; Liras, P. Heterologous expression of Streptomyces clavuligerus ATCC 27064 cephamycin C gene cluster. J. Biotechnol. 2014, 186, 21–29. [CrossRef] [PubMed]
80. Bellão, C.; Antonio, T.; Araujo, M.L.G.C.; Badino, A.C. Production of clavulanic acid and cephamycin C by Streptomyces clavuligerus under different fed-batch conditions. Braz. J. Chem. Eng. 2013, 30, 257–266. [CrossRef]
81. Cavallieri, A.P.; Baptista, A.S.; Leite, C.A.; Araujo, M.L.G.C. A case study in flux balance analysis: Lysine, a cephamycin C precursor, can also increase clavulanic acid production. Biochem. Eng. J. 2016, 112, 42–53. [CrossRef]
82. Li, R.; Townsend, C.A. Rational strain improvement for enhanced clavulanic acid production by genetic engineering of the glycolytic pathway in Streptomyces clavuligerus. Metab. Eng. 2006, 8, 240–252. [CrossRef] [PubMed]
83. Olano, C.; Lombó, F.; Méndez, C.; Salas, J.A. Improving production of bioactive secondary metabolites in actinomycetes by metabolic engineering. Metab. Eng. 2008, 10, 281–292. [CrossRef] [PubMed]
84. Adrio, J.L.; Demain, A.L. Recombinant organisms for production of industrial products. Bioeng. Bugs 2010, 1, 116–131. [CrossRef] [PubMed]
85. Hirata, D.B.; Oliveira, J.H.H.L.; Leão, K.V.; Rodrigues, M.I.; Ferreira, A.G.; Giulietti, M.; Barboza, M.; Hokka, C.O. Precipitation of clavulanic acid from fermentation broth with potassium 2-ethyl hexanoate salt. Sep. Purif. Technol. 2009, 66, 598–605. [CrossRef]
86. Higgens, C.E.; Kastner, R.E. Streptomyces clavuligerus sp. nova b-lactam antibiotic producer. Int. J. Syst. Evol. Microbiol. 1971, 21, 326–331. [CrossRef]
87. Brown, A.G.; Butterworth, D.; Cole, M.; Hanscomb, G.; Hood, J.D.; Reading, C.; Rolinson, G.N. Naturally occurring beta-lactamase inhibitors with antibacterial activity. J. Antibiot. 1976, 29, 668–669. [CrossRef] [PubMed]
88. Schmidt, F.R. Optimization and scale up of industrial fermentation processes. Appl. Microbiol. Biotechnol. 2005, 68, 425–435. [CrossRef] [PubMed]
89. Oliveira, J.H.L.; Granato, A.C.; Hirata, D.B.; Hokka, C.O.; Barboza, M. Clavulanic acid and cephamicin C: A perspective of the biosynthesis, isolation and action mechanism. Quim. Nova 2009, 32, 2142–2150. [CrossRef]
90. Townsend, C.A. New reactions in clavulanic acid biosynthesis. Curr Opin Chem Biol. 2002, 6, 583–589. [CrossRef]
91. Ser, H.L.; Law, J.W.F.; Chaiyakunapruk, N.; Jacob, S.A.; Palanisamy, U.D.; Chan, K.G.; Goh, B.H.; Lee, L.H. Fermentation conditions that affect clavulanic acid production in Streptomyces clavuligerus: A systematic review. Front. Microbiol. 2016, 7, 522. [CrossRef] [PubMed]
92. Domingues, L.C.G.; Teodoro, J.C.; Hokka, C.O.; Badino, A.C.; Araujo, M.L.G.C. Optimisation of the glycerol-to-ornithine molar ratio in the feed medium for the continuous production of clavulanic acid by Streptomyces clavuligerus. Biochem. Eng. J. 2010, 53, 7–11. [CrossRef]
93. Saudagar, P.S.; Singhal, R.S. Optimization of nutritional requirements and feeding strategies for clavulanic acid production by Streptomyces clavuligerus. Bioresour. Technol. 2007, 98, 2010–2017. [CrossRef] [PubMed]
94. Viana, D.A.; Carneiro-Cunha, M.N.; Araújo, J.M.; Barros-Neto, B.; Lima-Filho, J.L.; Converti, A.; Pessoa-Júnior, A.; Porto, A.L.F. Screening of variables influencing the clavulanic acid production by Streptomyces DAUFPE 3060 strain. Appl. Biochem. Biotechnol. 2010, 160, 1797–1807. [CrossRef] [PubMed]
95. Marques, D.A.V.; Carneiro da Cunha, M.N.; Araújo, J.M.; Lima-Filho, J.L.; Converti, A.; Pessoa, A., Jr.; Porto, A.L.F. Optimization of clavulanic acid production by Streptomyces DAUFPE 3060 by response surface methodology. Braz. J. Microbiol. 2011, 42, 658–667. [CrossRef] [PubMed]
96. Costa, C.L.L.; Badino, A.C. Production of clavulanic acid by Streptomyces clavuligerus in batch cultures without and with glycerol pulses under different temperature conditions. Biochem. Eng. J. 2012, 69, 1–7. [CrossRef]
97. Marques, D.A.V.; Santos-Ebinuma, V.C.; Oliveira, P.M.S.; Lima, G.M.S.; Araújo, J.M.; Lima-Filho, J.L.; Converti, A.; Pessoa-Júnior, A.; Porto, A.L.F. Screening of wild type Streptomyces isolates able to overproduce clavulanic acid. Braz. J. Microbiol. 2014, 45, 919–928. [CrossRef]
98. Saudagar, P.S.; Singhal, R.S. A statistical approach using L25 orthogonal array method to study fermentative production of clavulanic acid by Streptomyces clavuligerus MTCC1142. Appl. Biochem. Biotechnol. 2007, 136, 345–359. [CrossRef] [PubMed]
99. Salem-Berkhit, M.M.; Alanazi, F.K.; Alsarra, I.A. Improvement and enhancement of clavulanic acid production in Streptomyces clavuligerus using vegetable oils. Afr. J. Biotechnol. 2010, 9, 6806–6812.
100. Chen, K.C.; Lin, Y.H.; Tsai, C.M.; Hsieh, C.H.; Houng, J.Y. Optimization of glycerol feeding for clavulanic acid production by Streptomyces clavuligerus with glycerol feeding. Biotechnol. Lett. 2002, 24, 455–458. [CrossRef]
101. Thakur, R.; Roy, M.K.; Dutta, N.N.; Bezbaruah, R.L. Coordinate production of cephamycin c and clavulanic acid by Streptomyces clavuligerus. Indian J. Exp. Biol. 1999, 37, 1031–1033. [PubMed]
102. Teodoro, J.C.; Baptista-Neto, A.; Araujo, M.L.G.D.C.; Hokka, C.O.; Badino, A.C. Influence of glycerol and ornithine feeding on clavulanic acid production by Streptomyces clavuligerus. Braz. J. Chem. Eng. 2010, 27, 499–506. [CrossRef]
103. Vasconcelos, E.S.; Lima, V.A.; Goto, L.S.; Cruz-Hernández, I.L.; Hokka, C.O. Clavulanic acid production by the MMS 150 mutant obtained from wild type Streptomyces clavuligerus ATCC 27064. Braz. J. Microbiol. 2014, 44, 1049–1057. [CrossRef] [PubMed]
104. Baggaley, K.H.; Brown, A.G.; Schofield, C.J. Chemistry and biosynthesis of clavulanic acid and other clavams. Nat. Prod. Rep. 1997, 14, 309–333. [CrossRef] [PubMed]
105. Ives, P.R.; Bushell, M.E. Manipulation of the physiology of clavulanic acid production in Streptomyces clavuligerus. Microbiology 1997, 143, 3573–3579. [CrossRef] [PubMed]
106. Wang, Y.H.; Yang, B.; Ren, J.; Dong, M.L.; Liang, D.; Xu, A.L. Optimization of medium composition for the production of clavulanic acid by Streptomyces clavuligerus. Process Biochem. 2005, 40, 1161–1166. [CrossRef]
107. Teodoro, J.C.; Baptista-Neto, A.; Cruz-Hernandez, I.L.; Hokka, C.O.; Badino, A.C. Influence of feeding conditions on clavulanic acid production in fed-batch cultivation with medium containing glycerol. Appl. Microbiol. Biotechnol. 2006, 72, 450–455. [CrossRef] [PubMed]
108. Romero, J.; Liras, P.; Martin, J.F. Dissociation of cephamycin and clavulanic acid biosynthesis in Streptomyces clavuligerus. Appl. Microbiol. Biotechnol. 1984, 20, 318–325. [CrossRef]
109. Lee, P.C.; Ho, C.C. Production of clavulanic acid and cephamycin C by Streptomyces clavuligerus in palm-oil medium. World J. Microbiol. Biotechnol. 1996, 12, 73–75. [CrossRef] [PubMed]
110. Large, K.P.; Ison, A.P.; Williams, D.J. The effect of agitation rate on lipid utilisation and clavulanic acid production in Streptomyces clavuligerus. J. Biotechnol. 1998, 63, 111–119. [CrossRef]
111. Maranesi, G.L.; Baptista-Neto, A.; Hokka, C.O.; Badino, A.C. Utilization of vegetable oil in the production of clavulanic acid by Streptomyces clavuligerus ATCC 27064. World J. Microbiol. Biotechnol. 2005, 21, 509–514. [CrossRef]
112. Efthimiou, G.; Thumser, A.E.; Avignone−Rossa, C.A. A novel finding that Streptomyces clavuligerus can produce the antibiotic clavulanic acid using olive oil as a sole carbon source. J. Appl. Microbiol. 2008, 105, 2058–2064. [CrossRef] [PubMed]
113. Kim, S.J.; Kim, J.O.; Shin, C.H.; Park, H.W.; Kim, C.W. An approach to strain improvement and enhanced production of clavulanic acid in Streptomyces clavuligerus. Biosci. Biotech. Biochem. 2009, 73, 160–164. [CrossRef] [PubMed]
114. Stowell, J.D. The application of oils and fats in antibiotic processes. In Carbon Substrates in Biotechnology; Stowell, J.D., Beardsmore, A.J., Keevil, C.W., Woodward, J.R., Eds.; IRL Press: Oxford, UK, 1987; pp. 139–159.
115. Mayer, A.F.; Deckwer, W.D. Simultaneous production and decomposition of clavulanic acid during Streptomyces clavuligerus cultivations. Appl. Microbiol. Biotechnol. 1996, 45, 41–46. [CrossRef] [PubMed]
116. Joo, H.S.; Chang, C.S. Production of protease from a new alkalophilic Bacillus sp. I-312 grow on soybean meal: Optimization and some properties. Process Biochem. 2005, 40, 1263–1270. [CrossRef]
117. Romero, J.; Liras, P.; Martín, J.F. Utilization of ornithine and arginine as specific precursors of clavulanic acid. Appl. Environ. Microbiol. 1986, 52, 892–897. [PubMed]
118. Romero, J.; Liras, P.; Martín, J.F. Isolation and biochemical characterization of Streptomyces clavuligerus mutants in the biosynthesis of clavulanic acid and cephamycin C. Appl. Microbiol. Biotechnol. 1988, 27, 510–516. [CrossRef]
119. 3 unit. J. Am. Chem. Soc. 1985, 107, 1065–1066. [CrossRef]
120. De la Fuente, J.L.; Martin, J.F.; Liras, P. New type of hexameric ornithine carbamoyltransferase with arginase activity in the cephamycin producers Streptomyces clavuligerus and Nocardia lactamdurans. Biochem. J. 1996, 15, 173–179.
121. Valentine, B.P.; Bailey, C.R.; Doherty, A.; Morris, J.; Elson, S.W.; Baggaley, K.H.; Nicholson, N.H. Evidence that arginine is a later metabolic intermediate than ornithine in the biosynthesis of clavulanic acid by Streptomyces clavuligerus. Chem. Soc. Chem. Commun. 1993, 15, 1210–1211. [CrossRef]
122. Chen, K.C.; Lin, Y.H.; Wu, J.Y.; Hwang, S.C.J. Enhancement of clavulanic acid production in Streptomyces clavuligerus with ornithine feeding. Enzyme Microb. Technol. 2003, 32, 152–156. [CrossRef]
123. Barboza, M.; Almeida, R.M.; Hokka, C.O. Kinetic studies on clavulanic acid recovery by ion exchange chromatography. Bioseparation 2001, 10, 221–227. [CrossRef] [PubMed]
124. Albertsson, P.A. Partition of Cell Particles and Macromolecules, 3rd ed.; Wiley: New York, NY, USA, 1986.
125. Lima, C.A.; Freitas, A.C.V., Jr.; Lima Filho, J.L.; Converti, A.; Viana Marques, D.A.; Carneiro-da-Cunha, M.G.; Porto, A.L.F. Two-phase partitioning and partial characterization of a collagenase from Penicillium aurantiogriseum URM4622: Application to collagen hydrolysis. Biochem. Eng. J. 2013, 75, 64–71. [CrossRef]
126. Saravanan, S.; Rao, J.R.; Nair, B.U.; Ramasami, T. Aqueous two-phase poly(ethylene glycol)–poly(acrylic acid) system for protein partitioning: Influence of molecular weight, pH and temperature. Process Biochem. 2008, 43, 905–911. [CrossRef]
127. Viana Marques, D.A.; Pessoa-Júnior, A.; Lima-Filho, J.L.; Converti, A.; Perego, P.; Porto, A.L.F. Extractive fermentation of clavulanic acid by Streptomyces DAUFPE 3060 using aqueous two-phase system. Biotechnol. Prog. 2011, 27, 95–103. [CrossRef] [PubMed]
128. Silva, C.S.; Cuel, M.F.; Barreto, V.O.; Kwong, W.H.; Hokka, C.O.; Barboza, M. Separation of clavulanic acid from fermented broth of aminoacids by an aqueous two-phase system and ion-exchange adsorption. New Biotechnol. 2012, 29, 428–431. [CrossRef] [PubMed]
129. Lu, C.; Dong, J.; Yang, S.T. Butanol production from wood pulping hydrolysate in na integrated fermentation-gas stripping process. Bioresour. Technol. 2013, 143, 467–475. [CrossRef] [PubMed]
130. Lee, J.C.; Park, H.R.; Park, D.J.; Lee, H.B.; Kim, Y.B.; Kim, C.J. Improved production of teicoplanin using adsorbent resin in fermentations. Lett. Appl. Microbiol. 2003, 37, 196–200. [CrossRef] [PubMed]
131. Bersanetti, P.A.; Almeida, R.M.; Barboza, M.; Araújo, M.L.G.; Hokka, C.O. Kinetic studies on clavulanic acid degradation. Biochem. Eng. J. 2005, 23, 31–36. [CrossRef]
132. Panas, P.; Lopes, C.; Cerri, M.O.; Ventura, S.P.; Santos-Ebinuma, V.C.; Pereira, J.F. Purification of clavulanic acid produced by Streptomyces clavuligerus via submerged fermentation using polyethylene glycol/cholinium chloride aqueous two-phase systems. Fluid Phase Equilib. 2017, 450, 42–50. [CrossRef]
133. Smith, T.; Wolff, K.A.; Nguyen, L. Molecular biology of drug resistance in Mycobacterium tuberculosis. Curr. Top. Microbiol. Immunol. 2013, 374, 53–80. [CrossRef] [PubMed]
134. Cole, S.T. Inhibiting Mycobacterium tuberculosis within and without. Philos. Trans. R. Soc. B Biol. Sci. 2016, 371, 1–8. [CrossRef] [PubMed]
135. Wlodarchak, N.; Teachout, N.; Procknow, R.; Beczkiewicz, J.; Schaenzer, A.; Satyshur, K.; Pavelka, M.; Zuercher, B.; Drewry, D.; Sauer, J.D.; et al. Repurposed kinase inhibitors and β-lactams as a novel therapy for antibiotic resistant. BioRxiv 2017. [CrossRef]
136. Diacon, A.H.; van der Merwe, L.; Barnard, M.; von Groote-Bidlingmaier, F.; Lange, C.; Garcia-Basteiro, A.L.; Sevene, E.; Ballell, L.; Barros-Aguirre, D. Beta-Lactams against tuberculosis—New trick for an old dog? N. Engl. J. Med. 2016, 375, 393–394. [CrossRef] [PubMed]
137. Ramon-Garcia, S.; Gonzalez Del Rio, R.; Villarejo, A.S.; Sweet, G.D.; Cunningham, F.; Barros, D.; Ballell, L.; Mendoza-Losana, A.; Ferrer-Bazaga, S.; Thompson, C.J. Repurposing clinically approved cephalosporins for tuberculosis therapy. Sci. Rep. 2016, 6, 34293. [CrossRef] [PubMed]
138. Veziris, N.; Truffot, C.; Mainardi, J.L.; Jarlier, V. Activity of carbapenems combined with clavulanate against murine tuberculosis. Antimicrob. Agents Chemother. 2011, 55, 2597–2600. [CrossRef] [PubMed]
139. Nitsch-Osuch, A.; Kuchar, E.; Zycinska, K.; Gyrczuk, E.; Miskiewicz, K.; Korzeniewski, K. Implementation of hospital’s antibiotic policy decreases antimicrobial use in the general pediatric ward. Adv. Exp. Med. Biol. 2015, 857, 67–74. [CrossRef] [PubMed]
140. Urban, C.; Go, E.; Mariano, N.; Berger, B.J.; Avraham, I.; Rubin, D.; Rahal, J.J. Effect of sulbactam on infections caused by imipenem-resistant Acinetobacter calcoaceticus biotype anitratus. J. Infect. Dis. 1993, 167, 448–451. [CrossRef] [PubMed]
141. Brunetti, L.; Poustchi, S.; Cunningham, D.; Toscani, M.; Nguyen, J.; Lim, J.; Ding, Y.; Nahass, R.G. Clinical and economic impact of empirical extended-infusion piperacillin–Tazobactam in a community medical center. Ann. Pharmacother. 2015, 49, 754–760. [CrossRef] [PubMed]
142. Farrell, D.J.; Flamm, R.K.; Sader, H.S.; Jones, R.N. Antimicrobial activity of ceftolozane–Tazobactam tested against Enterobacteriaceae and Pseudomonas aeruginosa with various resistance patterns isolated in U.S. hospitals (2011–2012). Antimicrob. Agents Chemother. 2013, 57, 6305–6310. [CrossRef] [PubMed]
143. Sutherland, C.A.; Nicolau, D.P. Susceptibility profile of ceftolozane/tazobactam and other parenteral antimicrobials against Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa from US hospitals. Clin. Ther. 2015, 37, 1564–1571. [CrossRef] [PubMed]
144. Sader, H.S.; Farrell, D.J.; Castanheira, M.; Flamm, R.K.; Jones, R.N. Antimicrobial activity of ceftolozane/ tazobactam tested against Pseudomonas aeruginosa and Enterobacteriaceae with various resistance patterns isolated in European hospitals (2011–12). J. Antimicrob. Chemother. 2014, 69, 2713–2722. [CrossRef] [PubMed]
145. Estabrook, M.; Bussell, B.; Clugston, S.L.; Bush, K. In vitro activity of ceftolozane-tazobactam as determined by broth dilution and agar diffusion assays against recent U.S. Escherichia coli isolates from 2010 to 2011 carrying CTX-M-type extended-spectrum β-lactamases. J. Clin. Microbiol. 2014, 52, 4049–4052. [PubMed]
146. Solomkin, J.; Hershberger, E.; Miller, B.; Popejoy, M.; Friedland, I.; Steenbergen, J.; Yoon, M.; Collins, S.; Yuan, G.; Barie, P.S.; et al. Ceftolozane/tazobactam plus metronidazole for complicated intra-abdominal infections in an era of multidrug resistance: Results from a randomized, double-blind, phase 3 trial (ASPECT-cIAI). Clin. Infect. Dis. 2015, 60, 1462–1471. [CrossRef] [PubMed]
147. Kaur, R.; Gautam, V.; Singhal, L.; Ray, P. Antimicrobial activity of cefepime-tazobactam combination tested against clinical isolates of Enterobacteriaceae. J. Antibiot. 2014, 67, 603–604. [CrossRef] [PubMed]
148. Lahiri, S.D.; Mangani, S.; Jahic, H.; Benvenuti, M.; Durand-Reville, T.F.; De Luca, F.; Ehmann, D.E.; Rossolini, G.M.; Alm, R.A.; et al. Molecular basis of selective inhibition and slow reversibility of avibactam against class D carbapenemases: A structure-guided study of OXA-24 and OXA-48. ACS Chem. Biol. 2015, 10, 591–600. [CrossRef] [PubMed]
149. Li, H.; Estabrook, M.; Jacoby, G.A.; Nichols, W.W.; Testa, R.T.; Bush, K. In vitro susceptibility of characterized β-lactamase-producing strains tested with avibactam combinations. Antimicrob. Agents Chemother. 2015, 59, 1789–1793. [CrossRef] [PubMed]
150. Levasseur, P.; Girard, A.M.; Miossec, C.; Pace, J.; Coleman, K. In vitro antibacterial activity of the ceftazidime–avibactam combination against Enterobacteriaceae, including strains with well characterized β-lactamases. Antimicrob. Agents Chemother. 2015, 59, 1931–1934. [CrossRef] [PubMed]
151. Castanheira, M.; Mills, J.C.; Costello, S.E.; Jones, R.N.; Sader, H.S. Ceftazidime-avibactam activity tested against Enterobacteriaceae isolates from U.S. hospitals (2011 to 2013) and characterization of β-lactamase-producing strains. Antimicrob. Agents Chemother. 2015, 59, 3509–3517. [CrossRef] [PubMed]
152. Berkhout, J.; Melchers, M.J.; van Mil, A.C.; Nichols, W.W.; Mouton, J.W. In vitro activity of ceftazidime-avibactam combination in in vitro checkerboard assays. Antimicrob. Agents Chemother. 2015, 59, 1138–1144. [CrossRef] [PubMed]
153. Wang, X.; Zhang, F.; Zhao, C.; Wang, Z.; Nichols, W.W.; Testa, R.; Li, H.; Chen, H.; He, W.; Wang, Q.; et al. In vitro activities of ceftazidime-avibactam and aztreonam-avibactam against 372 Gram-negative bacilli collected in 2011 and 2012 from 11 teaching hospitals in China. Antimicrob. Agents Chemother. 2014, 58, 1774–1778. [CrossRef] [PubMed]
154. Sader, H.S.; Castanheira, M.; Flamm, R.K.; Farrell, D.J.; Jones, R.N. Antimicrobial activity of ceftazidime-avibactam against Gram-negative organisms collected from U.S. medical centers in 2012. Antimicrob. Agents Chemother. 2014, 58, 1684–1692. [CrossRef] [PubMed]
155. Flamm, R.K.; Sader, H.S.; Farrell, D.J.; Jones, R.N. Ceftazidime-avibactam and comparator agents tested against urinary tract isolates from a global surveillance program (2011). Diagn. Microbiol. Infect. Dis. 2014, 80, 233–238. [CrossRef] [PubMed]
156. Flamm, R.K.; Farrell, D.J.; Sader, H.S.; Jones, R.N. Ceftazidime/avibactam activity tested against Gram-negative bacteria isolated from bloodstream, pneumonia, intra-abdominal and urinary tract infections in US medical centres (2012). J. Antimicrob. Chemother. 2014, 69, 1589–1598. [CrossRef] [PubMed]
157. Sader, H.S.; Castanheira, M.; Flamm, R.K.; Mendes, R.E.; Farrell, D.J.; Jones, R.N. Ceftazidime/avibactam tested against Gram-negative bacteria from intensive care unit (ICU) and non-ICU patients, including those with ventilator-associated pneumonia. Int. J. Antimicrob. Agents 2015, 46, 53–59. [CrossRef] [PubMed]
158. Sader, H.S.; Castanheira, M.; Mendes, R.E.; Flamm, R.K.; Farrell, D.J.; Jones, R.N. Ceftazidime-avibactam activity against multidrug-resistant Pseudomonas aeruginosa isolated in U.S. medical centers in 2012 and 2013. Antimicrob. Agents Chemother. 2015, 59, 3656–3659. [CrossRef] [PubMed]
159. Testa, R.; Canton, R.; Giani, T.; Morosini, M.I.; Nichols, W.W.; Seifert, H.; Stefanik, D.; Rossolini, G.M.; Nordmann, P. In vitro activity of ceftazidime, ceftaroline and aztreonam alone and in combination with avibactam against European Gram-negative and Gram-positive clinical isolates. Int. J. Antimicrob. Agents 2015, 45, 641–646. [CrossRef] [PubMed]
160. Biedenbach, D.J.; Kazmierczak, K.; Bouchillon, S.K.; Sahm, D.F.; Bradford, P.A. In vitro activity of aztreonam–avibactam against a global collection of Gram-negative pathogens from 2012 and 2013. Antimicrob. Agents Chemother. 2015, 59, 4239–4248. [CrossRef] [PubMed]
161. Livermore, D.M.; Mushtaq, S.; Warner, M.; Zhang, J.; Maharjan, S.; Doumith, M.; Woodford, N. Activities of NXL104 combinations with ceftazidime and aztreonam against carbapenemase-producing Enterobacteriaceae. Antimicrob. Agents Chemother. 2011, 55, 390–394. [CrossRef] [PubMed]
162. Sader, H.S.; Farrell, D.J.; Flamm, R.K.; Jones, R.N. Activity of ceftaroline and comparator agents tested against Staphylococcus aureus from patients with bloodstream infections in US medical centres (2009–2013). J. Antimicrob. Chemother. 2015, 70, 2053–2056. [CrossRef] [PubMed]
163. Flamm, R.K.; Farrell, D.J.; Sader, H.S.; Jones, R.N. Antimicrobial activity of ceftaroline combined with avibactam tested against bacterial organisms isolated from acute bacterial skin and skin structure infections in United States medical centers (2010–2012). Diagn. Microbiol. Infect. Dis. 2014, 78, 449–456. [CrossRef] [PubMed]
164. Blizzard, T.A.; Chen, H.; Kim, S.; Wu, J.; Bodner, R.; Gude, C.; Imbriglio, J.; Young, K.; Park, Y.W.; Ogawa, A.; et al. Discovery of MK-7655, a β-lactamase inhibitor for combination with Primaxin®. Bioorg. Med. Chem. Lett. 2014, 24, 780–785. [CrossRef] [PubMed]
165. Morinaka, A.; Tsutsumi, Y.; Yamada, M.; Suzuki, K.; Watanabe, T.; Abe, T.; Furuuchi, T.; Inamura, S.; Sakamaki, Y.; Mitsuhashi, N.; et al. OP0595, a new diazabicyclooctane: Mode of action as a serine β-lactamase inhibitor, antibiotic and β-lactam ‘enhancer’. J. Antimicrob. Chemother. 2015, 70, 2779–2786. [CrossRef] [PubMed]
166. Lapuebla, A.; Abdallah, M.; Olafisoye, O.; Cortes, C.; Urban, C.; Quale, J.; Landman, D. Activity of meropenem combined with RPX7009, a novel β-lactamase inhibitor, against Gram-negative clinical isolates in New York City. Antimicrob. Agents Chemother. 2015, 59, 4856–4860. [CrossRef] [PubMed]
167. Crandon, J.L.; Nicolau, D.P. Comparative potency of cefepime (FEP) and cefepime/AAI101 (FEP/AAI101) against highly resistant Enterobacteriaceae. In Proceedings of the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Washington, DC, USA, 5–9 September 2014.
168. Crandon, J.L.; Nicolau, D.P. In vivo activities of simulated human doses of cefepime and cefepime–AAI101 against multidrug-resistant Gram-negative Enterobacteriaceae. Antimicrob. Agents Chemother. 2015, 59, 2688–2694. [CrossRef] [PubMed]
169. Chekan, J.R.; Cogan, D.P.; Nair, S.K. Molecular basis for resistance against phosphonate antibiotics and herbicides. MedChemComm 2016, 7, 28–36. [CrossRef] [PubMed]
170. Sogi, M.K.; Lien, K.A.; Johnson, J.R.; Krogan, N.J.; Stanley, S.A. The tyrosine kinase inhibitor Gefitinib restricts Mycobacterium tuberculosis growth through increased lysosomal biogenesis and modulation of cytokine signaling. ACS Infect. Dis. 2017, 3, 564–574. [CrossRef] [PubMed]
171. Pandey, R.; Kapur, R. Kinase inhibitors in clinical practice: An expanding world. J. Allergy Clin. Immunol. 2017, 141, 522–524. [CrossRef] [PubMed]
172. Stern, S.C.S.; Franken, L.; Voller, S.; Rentmeister, H.; Grosch, B. Breaking through the Wall: A Call for Concerted Action on Antibiotics Research and Development; The Boston Consulting Group: Berlin, Germany, 2017.
173. The Review on Antimicrobial Resistance. Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations; The Review on Antimicrobial Resistance: London, UK, 2014; pp. 1–20.
174. Bush, K. Antibacterial drug discovery in the 21st century. Clin. Microbiol. Infect. 2004, 10, 10–17. [CrossRef] [PubMed]
175. Projan, S.J. Why is big pharma getting out of antibacterial drug discovery? Drug Discov. Today 2003, 6, 427–430. [CrossRef]
176. Boggs, A.F.; Miller, G.H. Antibacterial drug discovery: Is small pharma the solution? Clin. Microbiol. Infect. 2004, 10, 32–36. [CrossRef] [PubMed]
177. Ferraro, J.S.; Towse, A.; Mestre-Ferrandiz, J. Incentives for New Drugs to Tackle Anti-Microbial Resistance; Office of Health Economics: London, UK, 2017.
178. The Pew Charitable Trusts. Antibiotics Currently in Clinical Development; The Pew Charitable Trusts: Philadelphia, PA, USA, 2017.
179. Simpkin, V.L.; Renwick, M.J.; Kelly, R.; Mossialos, E. Incentivising innovation in antibiotic drug discovery and development: Progress, challenges and next steps. J. Antibiot. 2017, 70, 1087–1096. [CrossRef] [PubMed]