review · Cell Communication and Signaling
Methicillin-resistant Staphylococcus aureus employs biofilm formation as a defensive and virulence strategy across healthcare, community, and livestock settings. Biofilm development relies on distinct molecular mechanisms: cell wall-anchored proteins enable initial attachment, extracellular polymeric substances form structural scaffolds, the cidABC operon regulates internal cell lysis, and proteases drive dispersal. Beyond standard attachment, maturation, and dispersal, the biofilm growth process includes multiplication and exodus stages. Intercellular communication occurs via quorum sensing regulated by the accessory gene regulator system using autoinducing peptides to coordinate virulence factor production. Quorum-sensing inhibitors display anti-virulence and antibiofilm activity, preventing colonisation on surfaces and tissues. To penetrate dense biofilm matrices, organic nanoparticles offer an effective carrier mechanism for therapeutic agents, circumventing the toxicity and non-degradability issues linked to metal-based nanoparticles. Combining organic nanocarriers with quorum inhibitors represents an emerging strategy against biofilm-mediated resistance.
Biofilms shield resistant bacterial superbugs from conventional antimicrobial treatments, enabling persistent infections to thrive across hospitals, communities, and livestock farms. Defining the precise molecular stages of biofilm growth and communication exposes critical vulnerabilities. Exploiting these targets using organic nanocarriers offers a way to penetrate protective bacterial matrices and tackle drug resistance without the toxicity challenges posed by older metal-based delivery systems.
This research informs the design of targeted nanotherapies, particularly combining organic nanoparticles with quorum inhibitors to disrupt resistant biofilms in clinical and veterinary settings. Potential beneficiaries include biotechnology companies and pharmaceutical developers addressing antimicrobial resistance. As the abstract describes a review of molecular mechanisms and proposed delivery strategies rather than tested formulations or clinical trials, the research sits at an early, conceptual stage far from real-world application.
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Methicillin-resistant Staphylococcus aureus (MRSA) represents a global threat, necessitating the development of effective solutions to combat this emerging superbug. In response to selective pressures within healthcare, community, and livestock settings, MRSA has evolved increased biofilm formation as a multifaceted virulence and defensive mechanism, enabling the bacterium to thrive in harsh conditions. This review discusses the molecular mechanisms contributing to biofilm formation across its developmental stages, hence representing a step forward in developing promising strategies for impeding or eradicating biofilms. During staphylococcal biofilm development, cell wall-anchored proteins attach bacterial cells to biotic or abiotic surfaces; extracellular polymeric substances build scaffolds for biofilm formation; the cidABC operon controls cell lysis within the biofilm, and proteases facilitate dispersal. Beside the three main sequential stages of biofilm formation (attachment, maturation, and dispersal), this review unveils two unique developmental stages in the biofilm formation process for MRSA; multiplication and exodus. We also highlighted the quorum sensing as a cell-to-cell communication process, allowing distant bacterial cells to adapt to the conditions surrounding the bacterial biofilm. In S. aureus, the quorum sensing process is mediated by autoinducing peptides (AIPs) as signaling molecules, with the accessory gene regulator system playing a pivotal role in orchestrating the production of AIPs and various virulence factors. Several quorum inhibitors showed promising anti-virulence and antibiofilm effects that vary in type and function according to the targeted molecule. Disrupting the biofilm architecture and eradicating sessile bacterial cells are crucial steps to prevent colonization on other surfaces or organs. In this context, nanoparticles emerge as efficient carriers for delivering antimicrobial and antibiofilm agents throughout the biofilm architecture. Although metal-based nanoparticles have been previously used in combatting biofilms, its non-degradability and toxicity within the human body presents a real challenge. Therefore, organic nanoparticles in conjunction with quorum inhibitors have been proposed as a promising strategy against biofilms. As nanotherapeutics continue to gain recognition as an antibiofilm strategy, the development of more antibiofilm nanotherapeutics could offer a promising solution to combat biofilm-mediated resistance.
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DOI: 10.1186/s12964-024-01511-2
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