Microbial interactions in facilitating antibiotic activity and resistance evolution

Abstract

In polymicrobial communities, microorganisms do not exist in isolation but engage in complex and dynamic interactions. Emerging evidence indicates that these microbial interactions can profoundly influence key aspects of antibiotic action, including antibiotic activity and the emergence and dissemination of antibiotic resistance. This mini-review examines the mechanistic pathways through which intra- and inter-specific interactions facilitate both individual and community-level responses to antibiotic treatment. Such interactions can also reshape the selective pressures imposed by antibiotics, thereby altering evolutionary trajectories toward resistance. We emphasize the importance of considering the ecological context of microbial communities as essential for advancing our understanding of antibiotic resistance and for developing more effective and sustainable antibiotic strategies.

Keywords: antibiotic activity; antibiotic resistance; ecological context; microbial interactions.

Fig 1

Direct and indirect interspecies interactions of microbial competition. (a) Contact-dependent interference includes mechanisms such as type VI secretion system-mediated killing. (b) Non-contact interactions include inhibition mediated by the secretion of antimicrobial metabolites. (c) Exploitation describes the competition for limited resources among microorganisms. Illustration created using BioRender.

Fig 2

Primary mechanisms of horizontal gene transfer (HGT) that enables bacteria to acquire resistance genes from other bacteria, facilitating rapid spread of antibiotic resistance. (a) Conjugation involves direct physical contact between donor and recipient cells, mediated by a conjugative pilus that facilitates the transfer of genetic material. (b) Transformation involves the uptake of free extracellular DNA from the environment by recipient cells, which can then incorporate the exogenous genetic material into their genomes. Illustration created using BioRender. (c) Transduction refers to the phage-mediated transfer of bacterial genetic material between cells.

Fig 3

Metabolic cross-feeding mediates indirect inter-species interaction. (a) Direct cross-feeding involves the mutual exchange of metabolites between microbial species. (b) Indirect cross-feeding occurs when one microbe uses a metabolite produced by another and subsequently modifies the environment in a way that benefits the original producer. Illustration created using BioRender.

Fig 4

Antibiotic inactivation-mediated cross-protection. (a) Secretion of antibiotic-degrading enzymes can generate cross-protection effect to susceptible neighboring bacteria. (b) Intracellular antibiotic modification involves the uptake and antibiotic neutralization of antibiotics to indirectly reduce antibiotic levels in the surrounding environment. Illustration created using BioRender.

Fig 5

Heterogeneous antibiotic diffusion in biofilms. The biofilm microenvironment is characterized by a descending gradient of oxygen and nutrient availability from the exterior toward its interior. This spatial gradient leads to reduced bacterial metabolic activity and increased antibiotic tolerance. Illustration created using BioRender.