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00925njm 22002777a 4500 dc Escobar-Salom, Maria author Barceló, Isabel María author Jordana-Lluch, Elena author Torrens, Gabriel author Oliver, Antonio author Juan, Carlos author 2023-03-10 Given 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. Escobar-Salom M, Barceló IM, Jordana-Lluch E, Torrens G, Oliver A, Juan C. Bacterial virulence regulation through soluble peptidoglycan fragments sensing and response: knowledge gaps and therapeutic potential. FEMS Microbiol Rev. 2023 Mar 10;47(2). 10.1093/femsre/fuad010 1574-6976 FEMS microbiology reviews https://hdl.handle.net/20.500.13003/18967 36893807 L640541348 2-s2.0-85151044357 https://hdl.handle.net/20.500.12105/23597 957800500003 Bacterial virulence regulation through soluble peptidoglycan fragments sensing and response: knowledge gaps and therapeutic potential