Contribution of quorum sensing to the virulence of Pseudomonas aeruginosa in pressure ulcer infection in rats
Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. Wound Repair and Regeneration
(Impact Factor: 2.75).
03/2011; 19(2):214-22. DOI: 10.1111/j.1524-475X.2010.00653.x
The impact of quorum sensing (QS) in in vivo models of infection has been widely investigated, but there are no descriptions for ischemic wound infection. To explore the role of QS in Pseudomonas aeruginosa in the establishment of ischemic wound infection, we challenged a pressure ulcer model in rats with the PAO-1, PAO-1 derivatives ΔlasIΔrhlI and ΔlasRΔrhlR strains, which cannot induce the virulence factor under QS control, thus the reduced tissue destruction was expended in these mutant strains. However unexpectedly, on postwounding day 3, the inflammatory responses in the three groups were similarly severe and the numbers of bacteria in tissue samples did not differ among the three strains. Biofilm formation was immature in QS-deficient strains, defined by the absence of dense bacterial aggregates and extracellular polymeric substance, which was confirmed by scanning electron microscopy. The Pseudomonas aeruginosa QS signal, acylated homoserine lactone, was only quantified from wound samples in the PAO-1 group. The swimming and twitching motilities were significantly enhanced in the ΔlasRΔrhlR group compared with the PAO-1 group in vitro. A significantly larger wound area was correlated with the bacterial motility. The inflammation in the early phase of bacterial challenge to wounds with immature biofilm formation in the QS-deficient strains indicated that the role of QS was more crucial for the chronic phase than for the acute phase of infection. The present findings indicate a difference in the importance of QS in ischemic wound infections compared with other infection models.
Figures in this publication
Available from: Olivera Stojadinovic
- "Our study has also shown the lack of Pseudomonas virulence factors and genes for QS molecules within wound isolates, which goes in line with previous studies  confirming that spontaneous QS- and virulence-deficient P. aeruginosa mutants are still capable of causing wound infections. Pseudomonas has two QS systems, LasI-LasR and RhlI-RhlR, shown to be important for wound infection and biofilm formation in rodent models , . Although we analyzed a small number of isolates, the lack of LasI in some and the presence of RhlI in all of the tested strains suggest that RhlI might be more important than LasI for cutaneous wound infections. "
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ABSTRACT: Understanding the pathology resulting from and 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 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 on wound healing. Wound re-epithelialization was significantly delayed by mixed-species biofilms through suppression of keratinocyte growth factor 1. showed an inhibitory effect on USA300 growth while both species co-existed in cutaneous wounds . Polymicrobial wound infection in the presence of 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 and for the first time, the contribution of virulence factors to the severity of polymicrobial wound infections.
PLoS ONE 02/2013; 8(2):e56846. DOI:10.1371/journal.pone.0056846 · 3.23 Impact Factor
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ABSTRACT: Data supporting the concept that microbial biofilms are a major cause of non-healing ulcers remain limited. A porcine model was established where delayed healing resulted from methicillin-resistant Staphylococcus aureus (MRSA) infection in full-thickness wounds. At the end of one study a wound remaining open was sampled and a MRSA strain was isolated. This pig-passaged strain was used as the inoculating strain in several subsequent studies. The resulting MRSA wound infections exhibited a greater, more stable tissue bioburden than seen in studies using the parent strain. Furthermore, wounds infected with the passaged strain experienced a greater delay in healing. To understand whether these changes corresponded to an increased biofilm character of the wound infection, wound biopsy samples from studies using either the parent or passaged MRSA strains were examined microscopically. Evidence of biofilm was observed for both strains, as most samples at a minimum had multiple isolated, dense microcolonies of bacteria. However, the passaged MRSA resulted in bacterial colonies of greater frequency and size that occurred more often in concatenated fashion to generate extended sections of biofilm. These results provide a model case in which increasing biofilm character of a wound infection corresponded with a greater delay in wound healing.
Wound Repair and Regeneration 06/2012; 20(4):537-43. DOI:10.1111/j.1524-475X.2012.00808.x · 2.75 Impact Factor
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ABSTRACT: Although bacterial biofilm is recognized as an important contributor to chronic wound pathogenesis, differences in biofilm virulence between species have never been studied in vivo.
Dermal punch wounds in New Zealand white rabbit ears were inoculated with Klebsiella pneumoniae, Staphylococcus aureus, or Pseudomonas aeruginosa, or left uninfected as controls. In vivo biofilm was established and maintained using procedures from our previously published wound biofilm model. Virulence was assessed by measurement of histologic wound healing and host inflammatory mediators. Scanning electron microscopy (SEM) and bacterial counts verified biofilm viability. Extracellular polymeric substance (EPS)-deficient P aeruginosa was used for comparison.
SEM confirmed the presence of wound biofilm for each species. P aeruginosa biofilm-infected wounds showed significantly more healing impairment than uninfected, K pneumoniae, and S aureus (p < 0.05), while also triggering the largest host inflammatory response (p < 0.05). Extracellular polymeric substance-deficient P aeruginosa demonstrated a reduced impact on the same quantitative endpoints relative to its wild-type strain (p < 0.05).
Our novel analysis demonstrates that individual bacterial species possess distinct levels of biofilm virulence. Biofilm EPS may represent an integral part of their distinct pathogenicity. Rigorous examination of species-dependent differences in biofilm virulence is critical to developing specific therapeutics, while lending insight to the interactions within clinically relevant, polybacterial biofilms.
Journal of the American College of Surgeons 06/2012; 215(3):388-99. DOI:10.1016/j.jamcollsurg.2012.05.028 · 5.12 Impact Factor
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