Bacterial virulence regulation through soluble peptidoglycan fragments sensing and response: knowledge gaps and therapeutic potential

Author:

Escobar-Salom María12,Barceló Isabel María12,Jordana-Lluch Elena1ORCID,Torrens Gabriel123,Oliver Antonio12,Juan Carlos12ORCID

Affiliation:

1. Research Unit and Microbiology Department, University Hospital Son Espases-Health Research Institute of the Balearic Islands (IdISBa) , Crtra. Valldemossa 79, 07010 Palma, Spain

2. Centro de Investigación Biomédica en Red, Enfermedades Infecciosas (CIBERINFEC). Av. Monforte de Lemos 3-5, 28029 , Madrid, Spain

3. Department of Molecular Biology and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå Centre for Microbial Research (UCMR), Umeå University. Försörjningsvägen 2A, SE-901 87 Umeå , Sweden

Abstract

AbstractGiven the growing clinical–epidemiological threat posed by the phenomenon of antibiotic resistance, new therapeutic options are urgently needed, especially against top nosocomial pathogens such as those within the ESKAPE group. In this scenario, research is pushed to explore therapeutic alternatives and, among these, those oriented toward reducing bacterial pathogenic power could pose encouraging options. However, the first step in developing these antivirulence weapons is to find weak points in the bacterial biology to be attacked with the goal of dampening pathogenesis. In this regard, during the last decades some studies have directly/indirectly suggested that certain soluble peptidoglycan-derived fragments display virulence-regulatory capacities, likely through similar mechanisms to those followed to regulate the production of several β-lactamases: binding to specific transcriptional regulators and/or sensing/activation of two-component systems. These data suggest the existence of intra- and also intercellular peptidoglycan-derived signaling capable of impacting bacterial behavior, and hence likely exploitable from the therapeutic perspective. Using the well-known phenomenon of peptidoglycan metabolism-linked β-lactamase regulation as a starting point, we gather and integrate the studies connecting soluble peptidoglycan sensing with fitness/virulence regulation in Gram-negatives, dissecting the gaps in current knowledge that need filling to enable potential therapeutic strategy development, a topic which is also finally discussed.

Funder

Balearic Islands Government

Ministerio de Ciencia e Innovación

Instituto de Salud Carlos III

European Regional Development Fund

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology

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