Probiotic nutrition is frequently claimed to improve human health. In particular, live probiotic bacteria obtained with food are believed to reduce pathogen colonization and thus, susceptibility to infection. However, the underlying mechanisms remain poorly understood. Here, we report that the consumption of probiotic Bacillus bacteria comprehensively abolishes colonization with the dangerous pathogen, Staphylococcus aureus . We discovered that the widespread fengycin class of Bacillus lipopeptides achieves colonization resistance by inhibiting the S. aureus Agr quorum-sensing signaling system. Our study presents a detailed molecular mechanism underlining the importance of probiotic nutrition in reducing infectious disease. Notably, we provide human evidence supporting the biological significance of probiotic bacterial interference and show for the first time that such interference can be achieved by blocking a pathogen’s signaling system. Furthermore, our findings suggest a probiotic-based method for S. aureus decolonization and new ways to fight S. aureus infections.

The emergence of a multidrug-resistant Candida species, C. auris and C. haemulonii, has been reported worldwide. In Thailand, information on them is limited. We collected clinical isolates from Thai patients with invasive candidiasis. Both species were compared with a laboratory C. albicans strain. In vitro antifungal susceptibility and thermotolerance, and pathogenesis in the zebrafish model of infection were investigated. Both species demonstrated high minimal inhibitory concentrations to fluconazole and amphotericin B. Only C. auris tolerated high temperatures, like C. albicans. In a zebrafish swim-bladder-inoculation model, the C. auris-infected group had the highest mortality rate and infectivity, suggesting the highest virulence. The case fatality rates of C. auris, C. haemulonii, and C. albicans were 100%, 83.33%, and 51.52%, respectively. Further immunological studies revealed that both emerging Candida species stimulated genes involved in the proinflammatory cytokine group. Interestingly, the genes relating to leukocyte recruitment were downregulated only for C. auris infections. Almost all immune response genes to C. auris had a peak response at an early infection time, which contrasted with C. haemulonii. In conclusion, both emerging species were virulent in a zebrafish model of infection and could activate the inflammatory pathway. This study serves as a stepping stone for further pathogenesis studies of these important emerging species.

Candidemia, a bloodstream infection caused by genus Candida, has a high mortality rate. Candida albicans was previously reported to be the most common causative species among candidemia patients. However, during the past 10 years in Thailand, Candida tropicalis has been recovered from blood more frequently than C. albicans. The cause of this shift in the prevalence of Candida spp. remains unexplored. We conducted in vitro virulence studies and antifungal susceptibility profiles of 48 C. tropicalis blood isolates collected during 2015-2017. To compare to global isolates of C. tropicalis, multilocus sequence typing (MLST), a minimum spanning tree, and an eBURST analysis were also conducted. C. tropicalis and C. albicans were the most (47-48.7%) and second-most (21.5-33.9%) common species to be isolated from candidemia patients, respectively. Of the C. tropicalis blood isolates, 29.2, 0, 100, and 93.8% exhibited proteinase activity, phospholipase activity, hemolytic activity, and biofilm formation, respectively. Moreover, 20.8% (10/48) of the isolates were resistant to voriconazole and fluconazole, and also showed high minimum inhibitory concentrations (MICs) to posaconazole and itraconazole. In contrast, most of the isolates were susceptible to anidulafungin (97.9%), micafungin (97.9%), and caspofungin (97.9%), and showed low MICs to amphotericin B (100%) and 5-flucytosine (100%). The MLST identified 22 diploid sequence types. Based on the eBURST analysis and minimum spanning tree, 9 out of 13 members (69.2%) of an eBURST group 3 were resistant to voriconazole and fluconazole, and also showed high MICs to posaconazole and itraconazole. Association analysis revealed the eBURST group 3 was significantly associated with the four triazole resistance (p < 0.001). In conclusion, the eBURST group 3 was associated with the triazole resistance and resistance to many antifungal drugs might be collectively responsible for the prevalence shift.