scholarly journals The evolution of virulence in Pseudomonas aeruginosa during chronic wound infection

2020 ◽  
Vol 287 (1937) ◽  
pp. 20202272
Author(s):  
Jelly Vanderwoude ◽  
Derek Fleming ◽  
Sheyda Azimi ◽  
Urvish Trivedi ◽  
Kendra P. Rumbaugh ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Wound Infection ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Morphological Diversity ◽  
Opportunistic Pathogen ◽  
Serial Passage ◽  
Multiple Infection ◽  
Evolution Of Virulence ◽  
Chronic Wound Infection

Opportunistic pathogens are associated with a number of chronic human infections, yet the evolution of virulence in these organisms during chronic infection remains poorly understood. Here, we tested the evolution of virulence in the human opportunistic pathogen Pseudomonas aeruginosa in a murine chronic wound model using a two-part serial passage and sepsis experiment, and found that virulence evolved in different directions in each line of evolution. We also assessed P. aeruginosa adaptation to a chronic wound after 42 days of evolution and found that morphological diversity in our evolved populations was limited compared with that previously described in cystic fibrosis (CF) infections. Using whole-genome sequencing, we found that genes previously implicated in P. aeruginosa pathogenesis ( lasR , pilR , fleQ , rpoN and pvcA ) contained mutations during the course of evolution in wounds, with selection occurring in parallel across all lines of evolution. Our findings highlight that: (i) P. aeruginosa heterogeneity may be less extensive in chronic wounds than in CF lungs; (ii) genes involved in P. aeruginosa pathogenesis acquire mutations during chronic wound infection; (iii) similar genetic adaptations are employed by P. aeruginosa across multiple infection environments; and (iv) current models of virulence may not adequately explain the diverging evolutionary trajectories observed in an opportunistic pathogen during chronic wound infection.

scholarly journals The evolution of virulence in Pseudomonas aeruginosa during chronic wound infection

2020 ◽  
Author(s):  
Jelly Vanderwoude ◽  
Derek Fleming ◽  
Sheyda Azimi ◽  
Urvish Trivedi ◽  
Kendra P. Rumbaugh ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Wound Infection ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Morphological Diversity ◽  
Opportunistic Pathogen ◽  
Serial Passage ◽  
Multiple Infection ◽  
Evolution Of Virulence ◽  
Chronic Wound Infection

ABSTRACTOpportunistic pathogens are associated with a number of chronic human infections, yet the evolution of virulence in these organisms during chronic infection remains poorly understood. Here, we tested the evolution of virulence in the human opportunistic pathogen Pseudomonas aeruginosa in a murine chronic wound model using a two-part serial passage and sepsis experiment, and found that virulence evolved in different directions in each line of evolution. We also assessed P. aeruginosa adaptation to a chronic wound after 42 days of evolution, and found that morphological diversity in our evolved populations was limited compared to that previously described in cystic fibrosis (CF) infections. Using whole genome sequencing, we found that genes previously implicated in P. aeruginosa pathogenesis (lasR, pilR, fleQ, rpoN, and pvcA), acquired mutations during the course of evolution in wounds, with some mutations evolving in parallel across all lines of evolution. Our findings highlight that (i) P. aeruginosa heterogeneity may be less extensive in chronic wounds than in CF lungs; (ii) genes involved in P. aeruginosa pathogenesis acquire mutations during chronic wound infection; (iii) similar genetic adaptations are employed by P. aeruginosa across multiple infection environments, and (iv) current models of virulence may not adequately explain the diverging evolutionary trajectories observed in an opportunistic pathogen during chronic wound infection.

Wound infections: an overview

2021 ◽  
Vol 26 (Sup6) ◽  
pp. S22-S25
Author(s):  
Martha Williams
Keyword(s):  
Wound Infection ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Wound Care ◽  
Economic Factors ◽  
Ageing Population ◽  
Wound Infections ◽  
The Many ◽  
Systemic Therapies ◽  
Socio Economic Factors

In the ever-changing world of wound care and nursing, it remains apparent that chronic wounds are a growing challenge. Evidence shows that age increases the likelihood of developing a chronic wound, which supports the notion that the burden of these wounds on the NHS is likely to further intensify with the ageing population. There are many reasons why a wound may fail to progress, including wound aetiology, comorbidities and environmental and socio-economic factors. One of the most significant reasons why wounds may fail to progress and become chronic is untreated wound infection. In order for clinicians to be able to treat and manage wound infections, it is vital that they understand how infection develops, the many ways in which infections may present themselves and how and when to initiate appropriate topical and systemic therapies to treat wound bed infections. The present article provides an overview of wound bed infections and their management.

scholarly journals Micro-management: curbing chronic wound infection

2016 ◽  
Vol 32 (4) ◽  
pp. 263-274 ◽  
Author(s):  
C. Withycombe ◽  
K.J. Purdy ◽  
S.E. Maddocks
Keyword(s):  
Wound Infection ◽  
Chronic Wound ◽  
Chronic Wound Infection

scholarly journals Frequency of quorum sensing mutations in Pseudomonas aeruginosa strains isolated from different environments

2021 ◽  
Author(s):  
Kathleen O’Connor ◽  
Conan Y. Zhao ◽  
Stephen P. Diggle
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Opportunistic Pathogen ◽  
Human Infection ◽  
Multiple Infection ◽  
Loss Of Function ◽  
Mutational Signatures ◽  
Amino Acid Length ◽  
Lung Infections

AbstractPseudomonas aeruginosa uses quorum sensing (QS) to coordinate the expression of multiple genes necessary for establishing and maintaining infection. lasR QS mutations have been shown to frequently arise in cystic fibrosis (CF) lung infections, however, there has been far less emphasis on determining whether QS system mutations arise across other environments. To test this, we utilized 852 publicly available sequenced P. aeruginosa genomes from the Pseudomonas International Consortium Database (IPCD) to study P. aeruginosa QS mutational signatures. We found that across all isolates, LasR is the most variable protein sequence compared to other QS proteins. In order to study isolates by source, we focused on a subset of 654 isolates collected from CF, wounds, and non-infection environmental isolates, where we could clearly identify their source. Using this sub-set analysis, we found that LasR mutations are not specific to CF lungs, but are common across all environments. We then used amino acid length as a proxy for observing loss of function in LasR proteins among the strains. We found that truncated LasR proteins are more abundant in P. aeruginosa strains isolated from human infection than the environment. Overall, our findings suggest that the evolution of lasR QS mutations in P. aeruginosa are common and not limited to infection environments.ImportancePseudomonas aeruginosa is an opportunistic pathogen which is often isolated from infection and environmental sources. P. aeruginosa uses quorum sensing (QS) to establish and adapt to infection environments. QS in P. aeruginosa is controlled by a complex hierarchical gene network in which the transcriptional regulator LasR has traditionally been thought to play a major controlling role. Despite this, lasR mutants are frequently isolated from chronic infection sites including the cystic fibrosis lung. Using an online P. aeruginosa strain database, we determined the frequency of mutation in key QS genes in multiple infection and non-infection environments and found that mutations and truncations in the lasR gene is more common than in other QS genes. Further, we found that lasR mutants are common in both infection and environmental strains. These findings further our understanding of QS in P. aeruginosa and have implications for the development of future therapies designed to inhibit QS.

scholarly journals MrkD1Pfrom Klebsiella pneumoniae Strain IA565 Allows for Coexistence with Pseudomonas aeruginosa and Protection from Protease-Mediated Biofilm Detachment

2013 ◽  
Vol 81 (11) ◽  
pp. 4112-4120 ◽  
Author(s):  
Brandon M. Childers ◽  
Tricia A. Van Laar ◽  
Tao You ◽  
Steven Clegg ◽  
Kai P. Leung
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Single Species ◽  
Wild Type ◽  
Content Type ◽  
Biofilm Model ◽  
Essential Components

ABSTRACTBiofilm formation and persistence are essential components for the continued survival of pathogens inside the host and constitute a major contributor to the development of chronic wounds with resistance to antimicrobial compounds. Understanding these processes is crucial for control of biofilm-mediated disease. Though chronic wound infections are often polymicrobial in nature, much of the research on chronic wound-related microbes has focused on single-species models.Klebsiella pneumoniaeandPseudomonas aeruginosaare microbes that are often found together in wound isolates and are able to form stablein vitrobiofilms, despite the antagonistic nature ofP. aeruginosawith other organisms. Mutants of theK. pneumoniaestrain IA565 lacking the plasmid-bornemrkD1Pgene were less competitive than the wild type in anin vitrodual-species biofilm model withP. aeruginosa(PAO1). PAO1 spent medium inhibited the formation of biofilm ofmrkD1P-deficient mutants and disrupted preestablished biofilms, with no effect on IA565 and no effect on the growth of the wild type or mutants. A screen using a two-allele PAO1 transposon library identified the LasB elastase as the secreted effector involved in biofilm disruption, and a purified version of the protein produced results similar to those with PAO1 spent medium. Various other proteases had a similar effect, suggesting that the disruption of themrkD1Pgene causes sensitivity to general proteolytic effects and indicating a role for MrkD1Pin protection against host antibiofilm effectors. Our results suggest that MrkD1Pallows for competition ofK. pneumoniaewithP. aeruginosain a mixed-species biofilm and provides defense against microbial and host-derived proteases.

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