Interactions of Methicillin Resistant Staphylococcus aureus USA300 and Pseudomonas aeruginosa in Polymicrobial Wound Infection

Abstract

Understanding the pathology resulting from Staphylococcus aureus and Pseudomonas aeruginosa polymicrobial wound infections is of great importance due to their ubiquitous nature, increasing prevalence, growing resistance to antimicrobial agents, and ability to delay healing. Methicillin-resistant S. aureus USA300 is the leading cause of community-associated bacterial infections resulting in increased morbidity and mortality. We utilized a well-established porcine partial thickness wound healing model to study the synergistic effects of USA300 and P. aeruginosa on wound healing. Wound re-epithelialization was significantly delayed by mixed-species biofilms through suppression of keratinocyte growth factor 1. Pseudomonas showed an inhibitory effect on USA300 growth in vitro while both species co-existed in cutaneous wounds in vivo. Polymicrobial wound infection in the presence of P. aeruginosa resulted in induced expression of USA300 virulence factors Panton-Valentine leukocidin and α-hemolysin. These results provide evidence for the interaction of bacterial species within mixed-species biofilms in vivo and for the first time, the contribution of virulence factors to the severity of polymicrobial wound infections.

Chronic Wound Biofilm Model

“…This was also a short-term study lasting for 4 days, which does not allow for the iterative microbe-host interplay toward a mature biofilm relevant to those present in chronic wounds. 47 All currently reported porcine models addressing biofilm infection address short-term acute-phase responses and therefore limited in power to understand long-term clinically relevant host-biofilm interaction. 25,45,46 Our interest in understanding the host response to chronic infection necessitated the development of a wound infection model that recapitulates the persistent nature of these types of wounds.…”

Iron Depletion Enhances Production of Antimicrobials by Pseudomonas aeruginosa

“…Many of these infections are polymicrobial, including those in diabetic foot ulcers (1,2) and chronic lung infections in cystic fibrosis (CF) patients (3,4). Several studies have noted that polymicrobial infections with P. aeruginosa are exacerbated compared to monoinfection (2,(5)(6)(7)(8)(9)(10). Thus, defining the mechanisms that mediate these microbial interactions is paramount to understanding the pathogenesis of polymicrobial infections.…”

Surface Potential Measurement of Bacteria Using Kelvin Probe Force Microscopy

“…MRSA has recently garnered status as a multi-drug resistant (MDR) "superbug" due to its naturally selected resistance to many β-lactam antibiotics and cephalosporins 21 . MRSA infections are now more challenging, difficult, and formidable to treat, leading to the use of harsher antimicrobials such as vancomycin or oxazolidinones which have higher toxicity levels in humans, and therefore cannot be used as long-term treatments 22 .…”