Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria

Abstract

Chronic and recurrent bacterial infections are frequently associated with the formation of biofilms on biotic or abiotic materials that are composed of mono- or multi-species cultures of bacteria/fungi embedded in an extracellular matrix produced by the microorganisms. Biofilm formation is, among others, regulated by quorum sensing (QS) which is an interbacterial communication system usually composed of two-component systems (TCSs) of secreted autoinducer compounds that activate signal transduction pathways through interaction with their respective receptors. Embedded in the biofilms, the bacteria are protected from environmental stress stimuli, and they often show reduced responses to antibiotics, making it difficult to eradicate the bacterial infection. Besides reduced penetration of antibiotics through the intricate structure of the biofilms, the sessile biofilm-embedded bacteria show reduced metabolic activity making them intrinsically less sensitive to antibiotics. Moreover, they frequently express elevated levels of efflux pumps that extrude antibiotics, thereby reducing their intracellular levels. Some efflux pumps are involved in the secretion of QS compounds and biofilm-related materials, besides being important for removing toxic substances from the bacteria. Some efflux pump inhibitors (EPIs) have been shown to both prevent biofilm formation and sensitize the bacteria to antibiotics, suggesting a relationship between these processes. Additionally, QS inhibitors or quenchers may affect antibiotic susceptibility. Thus, targeting elements that regulate QS and biofilm formation might be a promising approach to combat antibiotic-resistant biofilm-related bacterial infections.

Antimicrobial efficacy of extracts of Saudi Arabian desert Terfezia claveryi truffles

“…Quorum sensing also regulates the formation of biofilms such as the biofilm structure formation, dispersal of biofilm cells, and accumulation of biofilm biomass. It has also been suggested that auto-aggregation in the bacterial system may be promoted by quorum sensing ( Deng et al, 2020 , Sionov and Steinberg, 2022 ). Hence, the possible presence of anandamide in the T. claveryi methanolic and ethyl acetate extracts may explain the potent activity of these extracts on the biofilm of S. aureus IFO3060 ( Mukherjee and Bassler, 2019 ).…”

Conquering the host: Bordetella spp. and Pseudomonas aeruginosa molecular regulators in lung infection

“…Virulence GacS-GacA (Francis et al, 2017), SagS (Petrova and Sauer, 2011), BfiS-BfiR (Petrova and Sauer, 2009), HptB-HsbR (Bhuwan et al, 2012), LadS (Chambonnier et al, 2016), RetS (Moscoso et al, 2011), RocS2-RocA2 (Sivaneson et al, 2011), RocS1-RocR-RocA1 (Kuchma et al, 2005), PvrS-PvrR (Mikkelsen et al, 2013), ChpA/PilG/PilH/ChpB (Inclan et al, 2016), FimS (AlgZ)-AlgR (Okkotsu et al, 2014), PhoQ-PhoP (McPhee et al, 2006), ColS-ColR (Francis et al, 2017), AgtS-AgtR (Francis et al, 2017), PprA-PprB (de Bentzmann et al, 2012), CbrA-CbrB (Yeung et al, 2011) BvgAS (Roy et al, 1989) Colonization of lower respiratory tract SagS (Petrova and Sauer, 2011), HptB-HsbR (Bhuwan et al, 2012;Chambonnier et al, 2016), RocS2-RocA2 (Sivaneson et al, 2011), RoxS-RoxR (Hurley et al, 2010) PlrSR (Bone et al, 2017) Intracellular survival GacS-GacA (Francis et al, 2017), RoxS-RoxR (Hurley et al, 2010), RisAS (Jungnitz et al, 1998) Acute/chronic switch GacS-GacA (Bhagirath et al, 2017), CpxA-CpxR (Tian et al, 2016), KinA-AlgB (Chand et al, 2011(Chand et al, , 2012 Quorum sensing dependent regulation GacS-GacA (Francis et al, 2017), PhoR-PhoB (Bielecki et al, 2015), ParS-ParR (Wang et al, 2013), CzcS-CzcR (Sionov and Steinberg, 2022) Unknown Biofilm formation and maintenance BfiS-BfiR (Petrova and Sauer, 2009), SagS (Petrova and Sauer, 2011), LadS …”

The Antibacterial Effect of Cannabigerol toward Streptococcus mutans Is Influenced by the Autoinducers 21-CSP and AI-2

“…Several phenotypes in bacteria are controlled by the QS system. These phenotypes range from basic cell mobility to more complex communal interactions including biofilm formation, production of virulence factors, modulation of metabolic activity, production of extracellular polymeric substance (EPS), acquisition of nutrients, competence of genetic material, resistance to antibiotics and the generation of secondary metabolites [ 2 , 3 ].…”

“…This enables the reception of information regarding population and cellular density in the immediate surroundings. The activation of the signal transduction pathways leads to adapted alterations in gene expression [ 3 , 5 ].…”