Intracellular forms of menadione-dependent small-colony variants of methicillin-resistant Staphylococcus aureus are hypersusceptible to β-lactams in a THP-1 cell model due to cooperation between vacuolar acidic pH and oxidant species

Journal of Antimicrobial Chemotherapy

Volumn 67, Issue 12, 2012, Pages 2873-2881

  Garcia, Laetitia G ^a   Lemaire, Sandrine ^a   Kahl, Barbara C ^b   Becker, Karsten ^b   Proctor, Richard A ^c   Tulkens, Paul M ^a   Van Bambeke, Françoise ^a  

^a UNIVERSITÉ CATHOLIQUE DE LOUVAIN   (Belgium)

^b UNIVERSITY HOSPITAL MÜNSTER   (Germany)

^c UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

Author keywords

Cloxacillin; Doripenem; H2O2; Haemin; Meropenem

Indexed keywords

ACETYLCYSTEINE; ANTIBIOTIC AGENT; BACTERIAL PROTEIN; BETA LACTAM ANTIBIOTIC; CLOXACILLIN; DORIPENEM; HEMB PROTEIN; HYDROGEN PEROXIDE; MENADIONE; MENADIONE SODIUM BISULFITE; MEND PROTEIN; MEROPENEM; METICILLIN; OXIDIZING AGENT; OXYTETRACYCLINE; UNCLASSIFIED DRUG; VANCOMYCIN;

ACIDITY; ANTIBIOTIC SENSITIVITY; ARTICLE; BACTERIAL GROWTH; BACTERIAL STRAIN; BACTERICIDAL ACTIVITY; BACTERIUM ISOLATE; BROTH DILUTION; CELL LINE; CELL VACUOLE; COLONY FORMING UNIT; CONTROLLED STUDY; DRUG POTENCY; EXTRACELLULAR MATRIX; HILL REACTION; HUMAN; HUMAN CELL; IC 50; INCUBATION TIME; INOCULATION; INTRACELLULAR MEMBRANE; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; MINIMUM INHIBITORY CONCENTRATION; MUTANT; PENICILLIN RESISTANCE; PH; PHAGOCYTE; PHAGOCYTOSIS;

ANTI-BACTERIAL AGENTS; BETA-LACTAMS; CARBOXYLIC ACIDS; CELL LINE; COLONY COUNT, MICROBIAL; HUMAN EXPERIMENTATION; HUMANS; HYDROGEN-ION CONCENTRATION; METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS; MICROBIAL SENSITIVITY TESTS; MICROBIAL VIABILITY; MONOCYTES; OXIDANTS; PHAGOCYTOSIS; VACUOLES; VITAMIN K 3;

EID: 84869456191     PISSN: 03057453     EISSN: 14602091     Source Type: Journal    
DOI: 10.1093/jac/dks325     Document Type: Article

References (28)

1. Proctor RA, von Eiff C, Kahl BC et al. Small colony variants: a pathogenic form of bacteria that facilitates persistent and recurrent infections. Nat Rev Microbiol 2006; 4: 295-305.
2. Garcia LG, Lemaire S, Kahl BC et al. Pharmacodynamic evaluation of the activity of antibiotics against hemin- and menadione-dependent small-colony variants of Staphylococcus aureus in models of extracellular (broth) and intracellular (THP-1 monocytes) infections. Antimicrob Agents Chemother 2012; 56: 3700-11.
3. Bates DM, von Eiff C, McNamara PJ et al. Staphylococcus aureus menD and hemB mutants are as infective as the parent strains, but the menadione biosynthetic mutant persists within the kidney. J Infect Dis 2003; 187: 1654-61.
4. von Eiff C, Heilmann C, Proctor RA et al. A site-directed Staphylococcus aureus hemB mutant is a small-colony variant which persists intracellularly. J Bacteriol 1997; 179: 4706-12.
5. Lemaire S, Van Bambeke F, Mingeot-Leclercq MP et al. Role of acidic pH in the susceptibility of intraphagocytic methicillin-resistant Staphylococcus aureus strains to meropenem and cloxacillin. Antimicrob Agents Chemother 2007; 51: 1627-32.
6. Lemaire S, Olivier A, Van Bambeke F et al. Restoration of susceptibility of intracellular methicillin-resistant Staphylococcus aureus to b-lactams: comparison of strains, cells, and antibiotics. Antimicrob Agents Chemother 2008; 52: 2797-805.
7. Lemaire S, Fuda C, Van Bambeke F et al. Restoration of susceptibility of methicillin-resistant Staphylococcus aureus to b-lactam antibiotics by acidic pH: role of penicillin-binding protein PBP 2a. J Biol Chem 2008; 283: 12769-76.
8. Lannergard J, von Eiff C, Sander G et al. Identification of the genetic basis for clinical menadione-auxotrophic small-colony variant isolates of Staphylococcus aureus. Antimicrob Agents Chemother 2008; 52: 4017-22.
9. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing: Twenty-second Informational Supplement M100-S22. CLSI, Wayne, PA, USA, 2012.
10. Tsuchiya S, Yamabe M, Yamaguchi Y et al. Establishment and characterization of a human acute monocytic leukemia cell line (THP-1). Int J Cancer 1980; 26: 171-6.
11. Barcia-Macay M, Seral C, Mingeot-Leclercq MP et al. Pharmacodynamic evaluation of the intracellular activities of antibiotics against Staphylococcus aureus in a model of THP-1 macrophages. Antimicrob Agents Chemother 2006; 50: 841-51.
12. Allegra L, Dal Sasso M, Bovio C et al. Human neutrophil oxidative bursts and their in vitro modulation by different N-acetylcysteine concentrations. Arzneimittelforschung 2002; 52: 669-76.
13. Bergstrand H, Bjornson A, Eklund A et al. Stimuli-induced superoxide radical generation in vitro by human alveolar macrophages from smokers: modulation by N-acetylcysteine treatment in vivo. J Free Radic Biol Med 1986; 2: 119-27.
14. Villagrasa V, Cortijo J, Marti-Cabrera M et al. Inhibitory effects of N-acetylcysteine on superoxide anion generation in human polymorphonuclear leukocytes. J Pharm Pharmacol 1997; 49: 525-9.
15. Olivier AC, Lemaire S, Van Bambeke F et al. Role of rsbU and staphyloxanthin in phagocytosis and intracellular growth of Staphylococcus aureus in human macrophages and endothelial cells. J Infect Dis 2009; 200: 1367-70.
16. Rolinson GN, Sutherland R. The binding of antibiotics to serum proteins. Br J Pharmacol Chemother 1965; 25: 638-50.
17. Zhanel GG, Wiebe R, Dilay L et al. Comparative review of the carbapenems. Drugs 2007; 67: 1027-52.
18. Garcia LG, Lemaire S, Kahl BC et al. Influence of the protein kinase C activator, phorbol myristate acetate (PMA), on the intracellular activity of antibiotics against hemin and menadione auxotrophic small-colony variant (SCV) mutants of Staphylococcus aureus and their wild-type parental strain in human THP-1 cells. Antimicrob Agents Chemother 2012; doi:10.1128/AAC.01031-12.
19. Ekkelenkamp MB, Rooijakkers SHM, Bonten MJM. Staphylococci and micrococci. In: Cohen J, Powderly WG, Opal SM, eds. Infectious Diseases. Mosby/Elsevier, 2010.
20. Bylund J, Brown KL, Movitz C et al. Intracellular generation of superoxide by the phagocyte NADPH oxidase: how, where, and what for? Free Radic Biol Med 2010; 49: 1834-45.
21. Slauch JM. How does the oxidative burst of macrophages kill bacteria? Still an open question. Mol Microbiol 2011; 80: 580-3.
22. McNamara PJ, Proctor RA. Staphylococcus aureus small colony variants, electron transport and persistent infections. Int J Antimicrob Agents 2000; 14: 117-22.
23. Proctor RA, von Humboldt A. Bacterial energetics and antimicrobial resistance. Drug Resist Updat 1998; 1: 227-35.
24. von Eiff C, McNamara P, Becker K et al. Phenotype microarray profiling of Staphylococcus aureus menD and hemB mutants with the small-colony-variant phenotype. J Bacteriol 2006; 188: 687-93.
25. Wang X, Zhao X. Contribution of oxidative damage to antimicrobial lethality. Antimicrob Agents Chemother 2009; 53: 1395-402.
26. Kohanski MA, Dwyer DJ, Hayete B et al. A common mechanism of cellular death induced by bactericidal antibiotics. Cell 2007; 130: 797-810.
27. Gohring N, Fedtke I, Xia G et al. New role of the disulfide stress effector YjbH in b-lactam susceptibility of Staphylococcus aureus. Antimicrob Agents Chemother 2011; 55: 5452-8.
28. Singh VK, Utaida S, Jackson LS et al. Role for dnaK locus in tolerance of multiple stresses in Staphylococcus aureus. Microbiology 2007; 153: 3162-73.