The antimicrobial peptide-sensing system aps of Staphylococcus aureus.
Staphylococcus aureus is a leading cause of hospital-associated and, more recently, community-associated infections caused by highly virulent methicillin-resistant strains (CA-MRSA). S. aureus survival in the human host is largely defined by the ability to evade attacks by antimicrobial peptides (AMPs) and other mechanisms of innate host defence. Here we show that AMPs induce resistance mechanisms in CA-MRSA via the aps AMP sensor/regulator system, including (i) the d-alanylation of teichoic acids, (ii) the incorporation of lysyl-phosphatidylglycerol in the bacterial membrane and a concomitant increase in lysine biosynthesis, and (iii) putative AMP transport systems such as the vraFG transporter, for which we demonstrate a function in AMP resistance. In contrast to the aps system of S. epidermidis, induction of the aps response in S. aureus was AMP-selective due to structural differences in the AMP binding loop of the ApsS sensor protein. Finally, using a murine infection model, we demonstrate the importance of the aps regulatory system in S. aureus infection. This study shows that while significant interspecies differences exist in the AMP-aps interaction, the AMP sensor system aps is functional and efficient in promoting resistance to a variety of AMPs in a clinically relevant strain of the important human pathogen S. aureus.
Li
Min
M
Laboratory of Human Bacterial Pathogenesis, Genomics Unit, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Hamilton, Montana, USA.
Cha
David J
DJ
Lai
Yuping
Y
Villaruz
Amer E
AE
Sturdevant
Daniel E
DE
Otto
Michael
M
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism* / Q000494:pharmacology; D002352:Carrier Proteins / Q000096:biosynthesis; D002462:Cell Membrane / Q000378:metabolism; D017714:Community-Acquired Infections / Q000382:microbiology; D024881:Drug Resistance, Bacterial; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008239:Lysine / Q000096:biosynthesis; D016106:Methicillin Resistance; D051379:Mice; D012680:Sensitivity and Specificity; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000378:metabolism; D013682:Teichoic Acids / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; D002352:Carrier Proteins; D013682:Teichoic Acids; D008239:Lysine