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Review
. 2023 Dec 19:13:1327069.
doi: 10.3389/fcimb.2023.1327069. eCollection 2023.

A growing battlefield in the war against biofilm-induced antimicrobial resistance: insights from reviews on antibiotic resistance

Affiliations
Review

A growing battlefield in the war against biofilm-induced antimicrobial resistance: insights from reviews on antibiotic resistance

Liu Pai et al. Front Cell Infect Microbiol. .

Abstract

Biofilms are a common survival strategy employed by bacteria in healthcare settings, which enhances their resistance to antimicrobial and biocidal agents making infections difficult to treat. Mechanisms of biofilm-induced antimicrobial resistance involve reduced penetration of antimicrobial agents, increased expression of efflux pumps, altered microbial physiology, and genetic changes in the bacterial population. Factors contributing to the formation of biofilms include nutrient availability, temperature, pH, surface properties, and microbial interactions. Biofilm-associated infections can have serious consequences for patient outcomes, and standard antimicrobial therapies are often ineffective against biofilm-associated bacteria, making diagnosis and treatment challenging. Novel strategies, including antibiotics combination therapies (such as daptomycin and vancomycin, colistin and azithromycin), biofilm-_targeted agents (such as small molecules (LP3134, LP3145, LP4010, LP1062) _target c-di-GMP), and immunomodulatory therapies (such as the anti-PcrV IgY antibodies which _target Type IIIsecretion system), are being developed to combat biofilm-induced antimicrobial resistance. A multifaceted approach to diagnosis, treatment, and prevention is necessary to address this emerging problem in healthcare settings.

Keywords: antimicrobial resistance; biofilms; diagnosis; infections; treatment.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Life cycle of biofilm: Expanding the conceptual model of biofilm formation.
Figure 2
Figure 2
Mechanisms of resistance to antimicrobial agents in a biofilm,Created with BioRender.com. Schematic overview of the major mechanisms involved in antimicrobial resistance employed by bacterial biofilms. (1) The second messenger molecule, c-di-GMP, is associated with biofilm formation, virulence, and metabolic activity; Individual bacteria can synchronize their gene expression and alter their behaviour through chemical interactions between organisms in microbial communities, which is generally referred to as quorum sensing (QS)system. (2)N-Acyl homoserine lactones (AHLs) mediated QS system, the main QS systemin Gram-negative bacteria;(3) Autoinducer-2(AI-2) is the most common QS signal that mediated communication between intraspecies and interspecies; (4) Antibiotics-modifying enzymes induce resistance to multiple antibiotics, specially β-lactams, by transforming antimicrobials to a non-toxic form. (5) Efflux pump plays an important role in antibiotic resistance, including the efflux of the functional molecules (c-di-GMP, AHLs, AI-2 and antibiotics-modifying enzymes). extracellular polymeric substances (EPS), also efflux harmful ingredients (such as antibiotics and the metabolic intermediates) out of the bacteria. And is proven to be involved in the regulation of aggregation of the microcolonies and gene expression within biofilm; Horizontal gene transfer (HGT) is the process that passing antibiotic-resistant genes between bacterium. Here we present HGT in two ways: (6) conjugation between bacterium transmitted by plasmids and T4SS, (7) transduction between bacterium transmitted by bacteriophages. (8)T3SS in associated with phagocytic avoidance, cytotoxicity and systemic spread of bacteria. And is function by injecting effectors into the host cell directly, here we take effectors of Pseudomonas aeruginosa (ExoS, ExoT, ExoU, ExoY) as an example. (9) The components of EPS, including extracellular DNA, extracellular proteins and polysaccharides, hinder drug penetration and therefore cause drug resistance in biofilm.

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Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by Shenzhen Fund for Guangdong Provincial High-Level Clinical Key Specialties (No.SZGSP012); Shenzhen Key Medical Discipline Construction Fund (No. SZXK034).
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