In vivo modeling of biofilm-infected wounds: A review

Seth, Akhil K.; Geringer, Matthew R.; Hong, Seok Jong; Leung, Kai P.; Mustoe, Thomas A.; Galiano, Robert D.

doi:10.1016/j.jss.2012.06.048

Cited by 99 publications

(91 citation statements)

References 89 publications

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“…A future, extremely complex, goal will be to produce a faithful model of chronic wound infection, encompassing the plethora of microorganisms present clinically in wound biofilms. 76 In this study, we demonstrate the utility of our LPS model to explore the biological effects of oestrogen on 'infected' wounds. Indeed, these data provide the first evidence that oestrogen's beneficial influence on healing should apply to both infected and non-infected wounds, which has major clinical implications.…”

Section: Oestrogen Restores Healing In Lps Model R Crompton Et Almentioning

confidence: 80%

Oestrogen promotes healing in a bacterial LPS model of delayed cutaneous wound repair

Crompton

Williams

Ansell

et al. 2016

Laboratory Investigation

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Wound infection is a major clinical problem, yet understanding of bacterial host interactions in the skin remains limited. Microbe-derived molecules, known as pathogen-associated molecular patterns, are recognised in barrier tissues by pattern-recognition receptors. In particular, the pathogen-associated molecular pattern, lipopolysaccharide (LPS), a component of microbial cell walls and a specific ligand for Toll-like receptor 4, has been widely used to mimic systemic and local infection across a range of tissues. Here we administered LPS derived from Klebsiella pneumoniae, a species of bacteria that is emerging as a wound-associated pathogen, to full-thickness cutaneous wounds in C57/BL6 mice. Early in healing, LPS-treated wounds displayed increased local apoptosis and reduced proliferation. Subsequent healing progression was delayed with reduced re-epithelialisation, increased proliferation, a heightened inflammatory response and perturbed wound matrix deposition. Our group and others have previously demonstrated the beneficial effects of 17β-estradiol treatment across a range of preclinical wound models. Here we asked whether oestrogen would effectively promote healing in our LPS bacterial infection model. Intriguingly, co-treatment with 17β-estradiol was able to promote re-epithelialisation, dampen inflammation and induce collagen deposition in our LPS-delayed healing model. Collectively, these studies validate K. pneumoniae-derived LPS treatment as a simple yet effective model of bacterial wound infection, while providing the first indication that oestrogen could promote cutaneous healing in the presence of infection, further strengthening the case for its therapeutic use.

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Section: Oestrogen Restores Healing In Lps Model R Crompton Et Almentioning

confidence: 80%

Oestrogen promotes healing in a bacterial LPS model of delayed cutaneous wound repair

Crompton

Williams

Ansell

et al. 2016

Laboratory Investigation

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“…Many mammalian wound infection models have been developed such as, but not limited to, those that mimic human chronic and burn wound infections, and human pressure ulcers [112,113]. While many species of mammals have been used to model wound infections, rodents are by far the most common due to the benefits previously mentioned (e.g., cost and availability of genetic knockout strains).…”

Section: Skin and Soft Tissue Infectionsmentioning

confidence: 99%

Biofilm Models of Polymicrobial Infection

2015

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Interactions between microbes are complex and play an important role in the pathogenesis of infections. These interactions can range from fierce competition for nutrients and niches to highly evolved cooperative mechanisms between different species that support their mutual growth. An increasing appreciation for these interactions, and desire to uncover the mechanisms that govern them, has resulted in a shift from monomicrobial to polymicrobial biofilm studies in different disease models. Here we provide an overview of biofilm models used to study select polymicrobial infections and highlight the impact that the interactions between microbes within these biofilms have on disease progression. Notable recent advances in the development of polymicrobial biofilm-associated infection models and challenges facing the study of polymicrobial biofilms are addressed. Polymicrobial interactions in biofilmsOver the past 2 decades there has been a revolutionary paradigm shift in the field of microbiology with the appreciation that bacteria present in most biological systems exist in biofilms, rather than in a free-living state. This understanding has dramatically changed the way we study bacteria in the laboratory and resulted in the development of many new experimental systems that replicate biofilm environments [1][2][3][4][5]. Studies utilizing these systems have demonstrated time and time again that bacteria behave very differently when in a biofilm than during planktonic growth. In many ways, we now have to relearn everything we thought we knew about bacterial behavior through the view of the biofilm lens.Similarly, the recent explosion of metagenomic studies has significantly increased our appreciation of the complexity of the microbial populations present in biofilms [6,7]. This is also true for infections, most of which are thought to be biofilm related and inherently polymicrobial, including various species of bacteria, fungi and viruses [8]. It is thought that microbes act in concert to establish biofilms, which in turn can increase tolerance to antimicrobials, exacerbate of the host's immune response and increase persistence at the infection site [7,[9][10][11].Genetic diversity of microbes within biofilm communities is thought to increase the fitness of the residing community, making them more equipped to survive environmental stresses. In large part, this is due to an expanded gene pool, which can be more easily shared within the confines of a biofilm community [12]. Community composition and interactions within the community can have huge influences on bacterial behavior. Thus, just as the behavior of planktonic versus biofilm-associated bacteria is dramatically different, so is that of bacteria in single species versus multispecies systems.Interactions between microbes are complex and highly dependent on context. They can range from fierce competition for nutrients and niches, manifested by antagonistic behavior, to highly evolved cooperative mechanisms between different species that support their mutual grow...

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“…24 Studies on animals, including rats, mice, rabbits, and pigs, have mostly addressed short-term acute-phase processes ranging between 2 and 26 days of infection (Table 1). 7,10,[25][26][27][28][29] Such approaches are of limited value as they fail to capture the long-term interplay between the host and biofilm, which has a significant bearing of the wound microenvironment at the site of the infection. 17 This article aims to concisely and critically review the various in vitro and in vivo models used for the study of biofilm infections of wounds with specific emphasis on the preclinical porcine model of chronic infections (duration of 8 weeks) recently reported by our laboratory.…”

Section: Models Of Biofilm Infectionsmentioning

confidence: 99%

“…Outcomes such as impairment of epithelialization, overabundance of granulation tissue, and a hyperinflammatory state are interesting. 8,26,[40][41][42][43] However, reported studies involve short-term infection disallowing prolonged interaction between polymicrobial pathogens and the host. In that respect, the rabbit ear model suffers from limitations comparable to those discussed for the rodent models.…”

Section: In Vivo Biofilm Modelsmentioning

confidence: 99%