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Probiotics: their action against pathogens can be turned around.

ABSTRACT: Probiotics when applied in complex evolving (micro-)ecosystems, might be selectively beneficial or detrimental to pathogens when their prophylactic efficacies are prone to ambient interactions. Here, we document a counter-intuitive phenomenon that probiotic-treated zebrafish (Danio rerio) were respectively healthy at higher but succumbed at lower level of challenge with a pathogenic Vibrio isolate. This was confirmed by prominent dissimilarities in fish survival and histology. Based upon the profiling of the zebrafish microbiome, and the probiotic and the pathogen shared gene orthogroups (genetic niche overlaps in genomes), this consequently might have modified the probiotic metabolome as well as the virulence of the pathogen. Although it did not reshuffle the architecture of the commensal microbiome of the vertebrate host, it might have altered the probiotic-pathogen inter-genus and intra-species communications. Such in-depth analyses are needed to avoid counteractive phenomena of probiotics and to optimise their efficacies to magnify human and animal well-being. Moreover, such studies will be valuable to improve the relevant guidelines published by organisations such as FAO, OIE and WHO.

SUBMITTER: Gan L

PROVIDER: S-EPMC8225825 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The increasing emergence of antibiotic resistance is an urgent threat to global health care; thus, there is a need for new therapeutics. Guanidine is the preferred functional group for antimicrobial design and development. Herein, the potential antibacterial activity of the guanidine derivative isopropoxy benzene guanidine (IBG) against multidrug-resistant (MDR) bacteria was discovered. The synergistic antibacterial activity of IBG and colistin was determined by checkerboard assay, time-killing curve, and mouse experiments. The antibacterial mechanism of IBG was verified in fluorescent probe experiments, intracellular oxidative phosphorylation assays, and transcriptome analysis. The results showed that IBG displays efficient antibacterial activity against Gram-positive pathogens and Gram-negative pathogens with permeabilized outer membranes. Further mechanistic studies showed that IBG triggers cytoplasmic membrane damage by binding to phosphatidylglycerol and cardiolipin, leading to the dissipation of proton motive force and accumulation of intracellular ATP. IBG combined with low levels of colistin enhances bacterial outer membrane permeability and increases the accumulation of reactive oxygen species, as further evidenced by transcriptome analysis. Furthermore, the efficacy of IBG with colistin against MDR Escherichia coli in three infection models was demonstrated. Together, these results suggest that IBG is a promising adjuvant of colistin, providing an alternative approach to address the prevalent infections caused by MDR Gram-negative pathogens. IMPORTANCE As antibiotic discovery stagnates, the world is facing a growing menace from the emergence of bacteria that are resistant to almost all available antibiotics. The key to winning this race is to explore distinctive mechanisms of antibiotics. Thus, novel efficient antibacterial agents and alternative strategies are urgently required to fill the void in antibiotic development. Compared with the large amount of money and time required to develop new agents, the antibiotic adjuvant strategy is a promising approach to inhibit bacterial resistance and increase killing of bacteria. In this study, we found that the guanidine derivatives IBG not only displayed efficient antibacterial activities against Gram-positive bacteria but also restored colistin susceptibility of Gram-negative pathogens as an antibiotic adjuvant. More in-depth study showed that IBG is a potential lead to overcome antibiotic resistance, providing new insight into future antibiotic discovery and development.

Project description:The skin and its microbiota serve as physical barriers to prevent invasion of pathogens. Skin damage can be a consequence of illness, surgery, and burns. The most effective wound management strategy is to prevent infections, promote healing, and prevent excess scarring. It is well established that probiotics can aid in skin healing by stimulating the production of immune cells, and they also exhibit antagonistic effects against pathogens via competitive exclusion of pathogens. Our aim was to conduct a review of recent literature on the efficacy of using probiotics against pathogens that cause wound infections. In this integrative review, we searched through the literature published in the international following databases: PubMed, ScienceDirect, Web of Science, and Scopus using the search terms "probiotic" AND "wound infection." During a comprehensive review and critique of the selected research, fourteen in vitro studies, 8 animal studies, and 19 clinical studies were found. Two of these in vitro studies also included animal studies, yielding a total of 39 articles for inclusion in the review. The most commonly used probiotics for all studies were well-known strains of the species Lactobacillus plantarum, Lactobacillus casei, Lactobacillus acidophilus, and Lactobacillus rhamnosus. All in vitro studies showed successful inhibition of chosen skin or wound pathogens by the selected probiotics. Within the animal studies on mice, rats, and rabbits, probiotics showed strong opportunities for counteracting wound infections. Most clinical studies showed slight or statistically significant lower incidence of surgical site infections, foot ulcer infection, or burn infections for patients using probiotics. Several of these studies also indicated a statistically significant wound healing effect for the probiotic groups. This review indicates that exogenous and oral application of probiotics has shown reduction in wound infections, especially when used as an adjuvant to antibiotic therapy, and therefore the potential use of probiotics in this field remains worthy of further studies, perhaps focused more on typical skin inhabitants as next-generation probiotics with high potential.

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Probiotics: their action against pathogens can be turned around.

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