Cell wall active antibiotics reduce chromosomal DNA fragmentation by peptidoglycan hydrolysis in Staphylococcus aureus
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ORIGINAL PAPER
Cell wall active antibiotics reduce chromosomal DNA fragmentation by peptidoglycan hydrolysis in Staphylococcus aureus Marı´a Tamayo • Rebeca Santiso • Jaime Gosa´lvez Germa´n Bou • Marı´a del Ca´rmen Ferna´ndez • Jose´ Luis Ferna´ndez
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Received: 22 May 2012 / Revised: 27 June 2012 / Accepted: 29 June 2012 / Published online: 15 July 2012 Ó Springer-Verlag 2012
Abstract Lysostaphin digestion of peptidoglycan (PG) from Staphylococcus aureus resulted in chromosomal DNA fragmentation by released DNase, as directly visualized in situ on isolated nucleoids. Nevertheless, DNA digestion was partially prevented by previous incubation with antibiotics that inhibit PG synthesis. This inhibitory effect was much more remarkable with glycopeptides vancomycin and mainly teicoplanin than with beta-lactams cloxacillin and ceftazidime. Therefore, inhibition of PG chain elongation has a more significant inhibition of DNA degradation than inhibition of PG cross-linking, possibly due to a reduction in DNase storage at the cell wall. Keywords DNA fragmentation DNase Staphylococcus aureus Glycopeptides
Communicated by John Helmann. M. Tamayo R. Santiso J. L. Ferna´ndez (&) Genetics Unit, INIBIC-Complejo Hospitalario Universitario A Corun˜a (CHUAC), As Xubias, 84, 15006 A Corun˜a, Spain e-mail: [email protected]; [email protected] M. Tamayo R. Santiso J. L. Ferna´ndez Molecular Genetics and Radiobiology Laboratory, Centro Oncolo´gico de Galicia, 15009 A Corun˜a, Spain J. Gosa´lvez Genetics Unit, Facultad de Biologı´a, Universidad Auto´noma de Madrid, 28049 Madrid, Spain G. Bou M. C. Ferna´ndez Microbiology Division, INIBIC-Complejo Hospitalario Universitario A Corun˜a (CHUAC), 15006 A Corun˜a, Spain
Introduction DNA fragmentation may be not only a consequence of physical or chemical mutagens but may also be produced by biological agents. Staphylococcus aureus is a preeminent pathogen responsible for a wide spectrum of human and veterinary infections, and a great concern exists with respect to resistant strains such us community-acquired methicillin-resistant S. aureus, due to their increasing prevalence and pathogenicity. Many virulence factors correspond to multiple exoenzymes that are tissuedestructive and promote bacterial dissemination; among them is an extracellular thermostable DNase that has been classically recognized as a characteristic feature of S. aureus. Two types of thermostable nucleases, encoded by nuc1 and nuc2 genes, coexist in S. aureus (Tang et al. 2008). Extracellular DNA may be degraded by the DNase, possibly as a means to promote biofilm dispersal and subsequent bacterial spreading (Ranjit et al. 2009). Moreover, staphylococcal nuclease may also digest the nuclear DNA scaffold associated with antimicrobial peptides, histones and cell-specific proteases that constitute the neutrophil extracellular traps, which forms a matrix to entrap and kill microorganisms, thus contributing to resistance against entrapment (Berenders et al. 2010). From the technical p
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