Immune checkpoint inhibitors have been proposed as the standard treatment for different stages of non-small-cell lung cancer in multiple indications. Not all patients benefit from these treatments, however, and certain patients develop immune-related adverse events. Although the search for predictors of response to these drugs is a major field of research, these issues have yet to be resolved. It has been postulated that microbiota could play a relevant role in conditioning the response to cancer treatments; however, the human factor of intestinal permeability also needs to be considered as it is closely related to the regulation of host–microbiota interaction. In this article, we analyzed the possible relationship between the response to immune checkpoint inhibitors and the onset of immune-related adverse events, gut microbiota status, and intestinal membrane permeability. In a pioneering step, we also measured short-chain fatty acid content in feces. Although the correlation analyses failed to identify predictive biomarkers, even when all variables were integrated, our patients’ microbial gut ecosystems were rich and diverse, and the intestinal barrier’s integrity was preserved. These results add new knowledge on the composition of microbiota and its correlation with barrier permeability and short-chain fatty acids and suggest that more studies are required before these potential biomarkers can be incorporated into the clinical management of patients via immune checkpoint inhibitor treatment.

Global transcriptional regulators play key roles during bacterial adaptation to environmental fluctuations. Protein MafR from Enterococcus faecalis was shown to activate the transcription of many genes on a genome-wide scale. We proposed that MafR is a global regulator of the Mga/AtxA family. Here, we purified an untagged form of the MafR protein and found that it binds to linear double-stranded DNAs in a nonsequence-specific manner. Moreover, multiple MafR units (likely dieters) bind sequentially to the DNA molecule generating multimeric complexes. On DNAs that contain the promoter of the mafR gene, MafR recognizes a potentially curved DNA region. We discuss that a characteristic of the Mga/AtxA regulators might be their ability to recognize particular DNA shapes across the bacterial genomes.

Misuse and abuse of antibiotics on humans, cattle, and crops have led to the selection of multi-resistant pathogenic bacteria, the most feared ‘superbugs’. Infections caused by superbugs are progressively difficult to treat, with a subsequent increase in lethality: the toll on human lives is predicted to reach 10 million by 2050. Here we review three concepts linked to the growing resistance to antibiotics, namely (i) the Resistome, which refers to the collection of bacterial genes that confer resistance to antibiotics, (ii) the Mobilome, which includes all the mobile genetic elements that participate in the spreading of antibiotic resistance among bacteria by horizontal gene transfer processes, and (iii) the Nichome, which refers to the set of genes that are expressed when bacteria try to colonize new niches. We also discuss the strategies that can be used to tackle bacterial infections and propose an entente cordiale with the bacterial world so that instead of war and destruction of the ‘fierce enemy’ we can achieve a peaceful coexistence (the One Earth concept) between the human and the bacterial worlds. This, in turn, will contribute to microbial biodiversity, which is crucial in a globally changing climate due to anthropogenic activities.

Proteins that act as global transcriptional regulators play key roles in bacterial adaptation to new niches. These proteins recognize multiple DNA sites across the bacterial genome by different mechanisms. Enterococcus faecalis is able to survive in various niches of the human host, either as a commensal or as a leading cause of serious infections. Nonetheless, the regulatory pathways involved in its adaptive responses remain poorly understood. We reported previously that the MafR protein of E. faecalis causes genome-wide changes in the transcriptome. Here we demonstrate that MafR functions as a transcription activator. In vivo, MafR increased the activity of the P12294 and P11486 promoters and also the transcription levels of the two genes controlled by those promoters. These genes are predicted to encode a calcium-transporting P-type ATPase and a QueT transporter family protein, respectively. Thus, MafR could have a regulatory role in calcium homeostasis and queuosine synthesis. Furthermore, MafR recognized in vitro specific DNA sites that overlap the −35 element of each target promoter. The MafR binding sites exhibit a low sequence identity, suggesting that MafR uses a shape readout mechanism to achieve DNA-binding specificity.

We aimed to elucidate the cystic fibrosis (CF) microbiota composition (shotgun metagenomics) and functionality (short-chain fatty acids, SCFAs). Fecal and sputum samples were recruited from 39 clinically stable CF subjects. Bacillota and Pseudomonadota were dominant in both gut and lung compartments, whereas Ascomycota were the most abundant fungi in feces, and Basidiomycota, especially Malassezia globosa, in sputum. Viruses accounted for 0.4 % of the relative abundance in the gut and 0.6 % in lungs. Mycobacteroides abscessus was genetically identified in 10 individuals, although only 2 had positive cultures. Patients with higher levels of Pseudomonas filamentous phages had negative cultures for P. aeruginosa. The protozoan Toxoplasma gondii was detected in all sputum samples, accounting for 0.25 % of the metagenomic reads, with further PCR-confirmation in 50 % of subjects, including children. No correlation was found between SCFA and lung function or microbial composition. The resistome of the fecal compartment was higher than that of the lungs, and a greater abundance of SCFAs in the intestine was associated with poorer lung function. Patients with normal-mild lung function had higher alpha diversity in the respiratory microbiota; however, beta diversity in the stool was statistically different compared with the group with poorer lung function. Although there were no differences in SCFA concentrations, butyrate-producing bacteria were more abundant in the sputum of the group with better lung function. In fecal samples, resistome to tetracyclines, glycopeptides, and aminoglycosides predominated, whereas in sputum an enrichment of ARGs related to tetracyclines, beta-lactams, and macrolides was observed.