Therapeutic strategies against potential antibiofilm targets of multidrug‐resistant Acinetobacter baumannii

Abstract

Acinetobacter baumannii is the causative agent of various hospital‐acquired infections. Biofilm formation is one of the various antimicrobial resistance (AMR) strategies and is associated with high mortality and morbidity. Hence, it is essential to review the potential antibiofilm targets in A. baumannii and come up with different strategies to combat these potential targets. This review covers different pathways involved in the regulation of biofilm formation in A. baumannii like quorum sensing (QS), cyclic‐di‐GMP signaling, two‐component system (TCS), outer‐membrane protein (ompA), and biofilm‐associated protein (BAP). A newly discovered mechanism of electrical signaling‐mediated biofilm formation and contact‐dependent biofilm modulation has also been discussed. As biofilm formation and its maintenance in A. baumannii is facilitated by these potential targets, the detailed study of these targets and pathways can bring light to different therapeutic strategies such as anti‐biofilm peptides, natural and synthetic molecule inhibitors, QS molecule degrading enzymes, and other strategies. These strategies may help in suppressing the lethality of biofilm‐mediated infections. Targeting essential proteins/targets which are crucial for biofilm formation and regulation may render new therapeutic strategies that can aid in combating biofilm, thus reducing the recalcitrant infections and morbidity associated with the biofilm of A. baumannii.

Therapeutic Strategies against Biofilm Infections

“…Their recalcitrance poses a significant obstacle that conventional antimicrobials have not sufficiently addressed. It has become more difficult to implement eradication strategies due to biofilm spatial heterogeneity in terms of their chemical and microbial composition [ 168 , 169 ]. This study has reviewed a number of extremely novel antimicrobials based on nanotechnology and delivery methods for infection prevention, particularly in the context of improved penetration and targeted antimicrobial administration inside the biofilm.…”

Drug‑resistant Acinetobacter baumannii: From molecular mechanisms to potential therapeutics (Review)

“…The formation of Acinetobacter Baumannii is associated with the Quorum sensing pathway, two-component system signal transduction pathway, cyclic-di-GMP signaling and the capsular polysaccharide synthesis pathway. Biofilm-associated proteins such as Bap in Acinetobacter Baumannii also serve a vital role in biofilm (99). Several studies have shown that csuE, pgaB, epsA, ptk, bfmS and the ompA biofilm-related genes are involved in biofilm formation (99,100).…”

“…Biofilm-associated proteins such as Bap in Acinetobacter Baumannii also serve a vital role in biofilm (99). Several studies have shown that csuE, pgaB, epsA, ptk, bfmS and the ompA biofilm-related genes are involved in biofilm formation (99,100). However, resistance due to biofilms is specific and these genes are not direct factors for the resistance of Acinetobacter Baumannii (101).…”

Pharmacophore screening, denovo designing, retrosynthetic analysis, and combinatorial synthesis of a novel lead VTRA1.1 against RecA protein of Acinetobacter baumannii

“…baumannii and other nosocomial pathogens (Zhanel et al, 2007) but Acinetobacter has emerged as a resistant pathogen against it (Tiwari, Kapil, et al, 2012; Tiwari & Moganty, 2014; Tiwari & Rajeswari, 2013; Tiwari, Vashistt, et al, 2012; Vashist et al, 2011; Verma et al, 2017). It was also seen that reduced susceptibility to other biocides is also associated with co‐resistance to carbapenem (Fernandez‐Cuenca et al, 2015; Kawamura‐Sato et al, 2010) and biofilm formation (Kaushik, Tiwari, et al, 2022). Different antimicrobials have shown their antimicrobial activity by inducing ROS production, ultimately causing DNA damage (Fang, 2011; Imlay, 2008; Imlay & Linn, 1988), and destroying cell membrane and organelles (Nautiyal et al, 2014).…”