Biology subjects

Torrents, E.

Publications and source records attributed to Torrents, E..

4 recordsLinked to original sources

bioRxiv2024

Candida albicans enhance Staphylococcus aureus virulence by progressive generation of new phenotypes

Candida albicans and Staphylococcus aureus have been co-isolated from several biofilm- associated diseases, including those related to medical devices. This association confers advantages to both microorganisms, resulting in detrimental effects on the host. To elucidate this phenomenon, the present study investigated colony changes derived from non-physical interactions between C. albicans and S. aureus. We performed proximity assays by confronting colonies of the yeast and the bacteria on agar plates at six different distances for 9 days. We found that colony variants of S. aureus originated progressively after prolonged exposure to C. albicans proximity, specifically in response to pH neutralization of the media by the fungi. The new phenotypes of S. aureus were more virulent in a Galleria mellonella larvae model compared to colonies grown without C. albicans influence. This event was associated with an upregulation of RNAIII and AgrA expression, suggesting a role for -toxin. Our findings indicate that C. albicans enhances S. aureus virulence by inducing the formation of more aggressive colonies. ImportanceFor decades, it has been known that C. albicans increase S. aureus virulence, resulting in a "lethal synergism". However, it was only recently identified that this outcome is driven by the sustained activation of the staphylococcal agr system in response to C. albicans environmental modifications. Our experimental design allowed us to observe individual changes over time caused by the proximity of both microorganisms. As a result, we report for first time that C. albicans exposure induces the generation and favors the growth of S. aureus colony variants with increased expression of virulence factors. Our findings highlight the importance to understanding the intricate connection between environmental responses, virulence and fitness in S. aureus pathogenesis.

microbiology↗

bioRxiv2024

Antimicrobial and antibiofilm activity of human recombinant H1 histones against bacterial infections

Histones possess significant antimicrobial potential, yet their activity against biofilms remains underexplored. Moreover, concerns regarding adverse effects limit their clinical implementation. We investigated the antibacterial efficacy of human recombinant histone H1 subtypes against Pseudomonas aeruginosa PAO1, both planktonic and in biofilms. After the in vitro tests, toxicity and efficacy were assessed in a P. aeruginosa PAO1 infection model using Galleria mellonella larvae. Histones were also evaluated in combination with ciprofloxacin and gentamicin. Our results demonstrate antimicrobial activity against of all three histones against P. aeruginosa PAO1, with H1.0 and H1.4 showing efficacy at lower concentrations. The bactericidal effect was associated with a mechanism of membrane disruption. In vitro studies using static and dynamic models showed that H1.4 had antibiofilm potential by reducing cell biomass. Neither H1.0 nor H1.4 showed toxicity in G. mellonella larvae, and both increased larvae survival when infected with P. aeruginosa PAO1. Although in vitro synergism was observed between ciprofloxacin and H1.0, no improvement over the antibiotic alone was noted in vivo. Differences in antibacterial and antibiofilm activity were attributed to sequence and structural variations among histone subtypes. Moreover, the efficacy of H1.0 and H1.4 was influenced by the presence and strength of the extracellular matrix. These findings suggest histones hold promise for combating acute and chronic infections caused by pathogens such as P. aeruginosa. ImportanceThe constant increase of multidrug-resistant bacteria is a critical global concern. The inefficacy of current therapies to treat bacterial infections is attributed to multiple mechanisms of resistance, including the capacity to form biofilms. Therefore, the identification of novel and safe therapeutic strategies is imperative. This study confirms the antimicrobial potential of three histone H1 subtypes against both Gram-negative and Gram-positive bacteria. Furthermore, histones H1.0 and H1.4 demonstrated in vivo efficacy without associated toxicity in an acute infection model of Pseudomonas aeruginosa PAO1 in Galleria mellonella larvae. The bactericidal effect of these proteins also resulted in reduction in biomass of P. aeruginosa PAO1 biofilms. Given the clinical significance of this opportunistic pathogen, our research provides a comprehensive initial evaluation of the efficacy, toxicity, and mechanism of action of a potential new therapeutic approach against acute and chronic bacterial infections.

microbiology↗

bioRxiv2024

Interplay of Mycobacterium abscessus and Pseudomonas aeruginosa in coinfection: Biofilm Dynamics and Host Immune Response

The incidence of infection by nontuberculous mycobacteria, mainly Mycobacterium abscessus, in patients with cystic fibrosis and other chronic pulmonary illnesses is increasing, translating into an acceleration in the decline of lung function. In most cases, M. abscessus coinfects with Pseudomonas aeruginosa, the most common pathogen in these chronic diseases. However, it is unknown how these two bacterial species interact when coinfecting. This study aims to explore the behavior of both species in three relevant pathogenic settings: dual-species biofilm development using a recently developed method to monitor individual species in dual-species biofilms; coinfection in bronchial epithelial cells using in vitro assays; and in vivo coinfection using the Galleria mellonella model. The results demonstrate the capability of both species to form stable mixed biofilms and to reciprocally inhibit single-biofilm progression. Coinfections in bronchial epithelial cells were correlated with significantly decreased cell viability, while in G. mellonella, coinfections induced lower survival rates than individual infections. Outstandingly, the analysis of the immune response triggered by each bacterium in bronchial epithelial cell assays and G. mellonella larvae revealed that P. aeruginosa induces the overexpression of proinflammatory and melanization cascade responses, respectively. In contrast, M. abscessus and P. aeruginosa coinfection significantly inhibited the immune response in both models, resulting in worse consequences for the host than those generated by single P. aeruginosa infection. Overall, the presence of M. abscessus produces a decline in the immune responses that worsens the infection and compromises the host. ImportanceThe appearance of bacterial infections in the respiratory tract of patients with chronic respiratory diseases suppose a serious and difficult to treat health problem. This complication is exacerbated by the increase resistance against antibiotics generated by pathogenic microorganisms. The most common and virulent pathogenic bacteria reported in the respiratory airway is Pseudomonas aeruginosa. It is a Gram-negative, ubiquitous, and intrinsic resistant to antibiotics bacteria. However, the incidence of a rapidly growing, multi-drug resistant mycobacteria; Mycobacterium abscessus, is growing worldwide. The pulmonary coinfection by both pathogens is directly related with higher rates of morbidity and mortality of patients. The significance of our research is characterizing the behavior of these two pathogens when they coinfects together, exploring the immune response triggered by the host and its impact in the survival. The purpose is enhancing the limited understanding we have of this clinically relevant coinfection to favor the development of new effective treatments.

microbiology↗

bioRxiv2022

Genomic analysis of Mycobacterium brumae sustains its nonpathogenic and immunogenic phenotype

M. brumae is a rapid-growing, non-pathogenic Mycobacterium species, originally isolated from environmental and human samples in Barcelona, Spain. M. brumae is not pathogenic and its in vitro phenotype and immunogenic properties have been well characterized. However, the knowledge of its underlying genetic composition is still incomplete. In this study, we first describe the 4 Mb genome of the M. brumae type strain ATCC 51384T assembling PacBio reads, and second, we assess the low intraspecies variability by comparing the type strain with Illumina reads from three additional strains. M. brumae genome is composed of a circular chromosome with a high GC content of 69.2 % and containing 3,791 CDSs, 97 pseudogenes, one prophage and no CRISPR loci. M. brumae has shown no pathogenic potential in in vivo experiments, and our genomic analysis confirms its phylogenetic position with other non-pathogenic and rapid growing mycobacteria. Accordingly, we determined the absence of virulence related genes, such as ESX-1 locus and most PE/PPE genes, among others. Although immunogenic potential of M. brumae was proved to be as high as Mycobacterium bovis BCG, the only mycobacteria licensed to treat cancer, the genomic content of M. tuberculosis T cell and B cell antigens in M. brumae is considerably lower than those of M. bovis BCG. Overall, this work provides relevant genomic data on one of the species of the mycobacterial genus with high therapeutic potential.

genetics↗