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A Gram-negative pink-pigmented bacillus (named 2A) was isolated from L. cv. Desirée plants that were strikingly more developed, presented increased root hair density, and higher biomass than other potato lines of the same age. The 16S ribosomal DNA sequence, used for comparative gene sequence analysis, indicated that strain 2A belongs to the genus . Nucleotide identity between sp. 2A sequenced genome and the rest of the species that belong to the genus suggested that this species has not been described so far. potato plants inoculated with sp. 2A had a better performance when grown under 50 mM NaCl or when infected with . We inoculated sp. 2A in roots and exposed these plants to salt stress (75 mM NaCl). sp. 2A-inoculated plants, grown in control or salt stress conditions, displayed a higher density of lateral roots (p < 0.05) compared to noninoculated plants. Moreover, under salt stress, they presented a higher number of leaves and larger rosette diameter. In dual confrontation assays, sp. 2A displayed biocontrol activity against , , and , but not against , and . In addition, we observed that sp. 2A diminished the size of necrotic lesions and reduced chlorosis when greenhouse potato plants were infected with . sp. 2A produces indole acetic acid, solubilizes mineral phosphate and is able to grow in a N free medium. Whole-genome sequencing revealed metabolic pathways associated with its plant growth promoter capacity. Our results suggest that sp. 2A is a plant growth-promoting rhizobacteria (PGPR) that can alleviate salt stress, and restricts infection in potato plants, emerging as a potential strategy to improve crop management.

Background Tuberculosis (TB), caused by the intracellular bacterium Mycobacterium tuberculosis complex (Mtbc), remains a significant global health challenge, with Mtbc once again being the leading infectious killer worldwide. Despite over a century of research, the disease continues to pose a major threat, with an estimated one-fourth of the global population latently infected. According to the World Health Organization (WHO), approximately 1.3 million deaths were attributed to TB in 2024 alone. The emergence of multidrug-resistant (MDR) strains, resistant to isoniazid and rifampicin, and extensively drug-resistant (XDR) strains, resistant to rifampicin (and may also be resistant to isoniazid), to at least one fluoroquinolone (levofloxacin or moxifloxacin) and to at least one other Group A drug (bedaquiline or linezolid), further complicates the situation, posing significant challenges for healthcare systems. While the WHO definition of XDR-TB has recently been updated, in this study we applied the classification in effect during the 2006–2015 period, when the isolates were collected and characterized. In Argentina, TB burden is moderate compared to other countries, with approximately 10,500 new cases and 1,000 deaths reported annually. While standard therapy is generally effective, XDR Mtb infections require prolonged and costly treatment and are often associated with a guarded prognosis. Methods In this work, we applied whole-genome sequencing analysis to characterise XDR-TB strains circulating in Argentina between 2006 and 2015. Genotypic variants of each isolate were compared against resistance-associated variant databases and subjected to local and global phylogenetic analyses. Results The analysis revealed no common origins for the most frequently observed resistance mutations. Notable variants associated with resistance to first-line drugs included katG Ser315Thr and fabG1 -15C < T for isoniazid, rpoB Ser450Leu and Asp435Val for rifampin, embB Gly406Ala, and Met306Ile for ethambutol, as well as multiple variants in the pncA gene linked to pyrazinamide resistance. Conclusions This study provides valuable insights into the molecular mechanisms of antibiotic resistance in M. tuberculosis , specifically focusing on XDR strains circulating in Argentina. The findings highlight the genetic diversity and complexity of resistance-associated variants, emphasizing the need for continued research and surveillance efforts to address this pressing global health threat. Clinical trial number Not applicable.

Decades of successful use of antibiotics is currently challenged by the emergence of increasingly resistant bacterial strains. Novel drugs are urgently required but, in a scenario where private investment in the development of new antimicrobials is declining, efforts to combat drug-resistant infections become a worldwide public health problem. Reasons behind unsuccessful new antimicrobial development projects range from inadequate selection of the molecular targets to a lack of innovation. In this context, increasingly available omics data for multiple pathogens has created new drug discovery and development opportunities to fight infectious diseases. Identification of an appropriate molecular target is currently accepted as a critical step of the drug discovery process. Here, we review how diverse layers of multi-omics data in conjunction with structural/functional analysis and systems biology can be used to prioritize the best candidate proteins. Once the target is selected, virtual screening can be used as a robust methodology to explore molecular scaffolds that could act as inhibitors, guiding the development of new drug lead compounds. This review focuses on how the advent of omics and the development and application of bioinformatics strategies conduct a “big-data era” that improves target selection and lead compound identification in a cost-effective and shortened timeline.

Background Whole-genome sequencing has shown that the Mycobacterium tuberculosis infection process can be more heterogeneous than previously thought. Compartmentalized infections, exogenous reinfections, and microevolution are manifestations of this clonal complexity. The analysis of the mechanisms causing the microevolution —the genetic variability of M. tuberculosis at short time scales— of a parental strain into clonal variants with a patient is a relevant issue that has not been yet completely addressed. To our knowledge, a whole genome sequence microevolution analysis in a single patient with inadequate adherence to treatment has not been previously reported. Case presentation In this work, we applied whole genome sequencing analysis for a more in-depth analysis of the microevolution of a parental Mycobacterium tuberculosis strain into clonal variants within a patient with poor treatment compliance in Argentina. We analyzed the whole-genome sequence of 8 consecutive Mycobacterium tuberculosis isolates obtained from a patient within 57-months of intermittent therapy . Nineteen mutations (9 short-term, 10 fixed variants) emerged, most of them associated with drug resistance. The first isolate was already resistant to isoniazid, rifampicin, and streptomycin, thereafter the strain developed resistance to fluoroquinolones and pyrazinamide. Surprisingly, isolates remained susceptible to the pro-drug ethionamide after acquiring a frameshift mutation in ethA, a gene required for its activation. We also found a novel variant, (T-54G), in the 5′ untranslated region of whiB7 (T-54G), a region allegedly related to kanamycin resistance. Notably, discrepancies between canonical and phage-based susceptibility testing to kanamycin were previously found for the isolate harboring this mutation. In our patient, microevolution was mainly driven by drug selective pressure. Rare short-term mutations fixed together with resistance-conferring mutations during therapy. Conclusions This report highlights the relevance of whole-genome sequencing analysis in the clinic for characterization of pre-XDR and MDR resistance profile, particularly in patients with incomplete and/or intermittent treatment.

Carbapenem-resistant Klebsiella pneumoniae (CR-KP) represents an emerging threat to public health. CR-KP infections result in elevated morbidity and mortality. This fact, coupled with their global dissemination and increasingly limited number of therapeutic options, highlights the urgency of novel antimicrobials. Innovative strategies linking genome-wide interrogation with multi-layered metabolic data integration can accelerate the early steps of drug development, particularly target selection. Using the BioCyc ontology, we generated and manually refined a metabolic network for a CR-KP, K. pneumoniae Kp13. Converted into a reaction graph, we conducted topological-based analyses in this network to prioritize pathways exhibiting druggable features and fragile metabolic points likely exploitable to develop novel antimicrobials. Our results point to the aptness of previously recognized pathways, such as lipopolysaccharide and peptidoglycan synthesis, and casts light on the possibility of targeting less explored cellular functions. These functions include the production of lipoate, trehalose, glycine betaine, and flavin, as well as the salvaging of methionine. Energy metabolism pathways emerged as attractive targets in the context of carbapenem exposure, targeted either alone or in conjunction with current therapeutic options. These results prompt further experimental investigation aimed at controlling this highly relevant pathogen.

Leishmaniasis is a public health disease that requires the development of more effective treatments and the identification of novel molecular targets. Since blocking the PI3K/AKT pathway has been successfully studied as an effective anticancer strategy for decades, we examined whether the same approach would also be feasible in Leishmania due to their high amount and diverse set of annotated proteins. Here, we used a best reciprocal hits protocol to identify potential protein kinase homologues in an annotated human PI3K/AKT pathway. We calculated their ligandibility based on available bioactivity data of the reported homologues and modelled their 3D structures to estimate the druggability of their binding pockets. The models were used to run a virtual screening method with molecular docking. We found and studied five protein kinases in five different Leishmania species, which are AKT, CDK, AMPK, mTOR and GSK3 homologues from the studied pathways. The compounds found for different enzymes and species were analysed and suggested as starting point scaffolds for the design of inhibitors. We studied the kinases’ participation in protein–protein interaction networks, and the potential deleterious effects, if inhibited, were supported with the literature. In the case of Leishmania GSK3, an inhibitor of its human counterpart, prioritized by our method, was validated in vitro to test its anti-Leishmania activity and indirectly infer the presence of the enzyme in the parasite. The analysis contributes to improving the knowledge about the presence of similar signalling pathways in Leishmania, as well as the discovery of compounds acting against any of these kinases as potential molecular targets in the parasite.

Clostridioides difficile is a gram-positive bacterium implicated in antibiotic-associated diarrhea. The use of antibiotics alters the gut microbiota, rendering the host susceptible to infection by C. difficile. This pathogen colonizes the large intestine of humans and animals leading to asymptomatic carriage or clinical manifestations such as toxic megacolon and fulminant colitis depending on a wide range of pathogen and host factors. The emergence of BI/NAP1/027 strains in North America and the spread of these hypervirulent ribotypes worldwide have been linked to the increase in incidence and severity of C. difficile infections (CDI) over the last decade. In this work, we aimed to characterize the BI/NAP1/027 C. difficile commercial strain CDC20121308 widely employed in the study of host-pathogen interactions. The genome sequence was obtained using a whole-genome shotgun strategy. A total of 3,717 coding sequences (CDS) and 45 tRNAs were predicted. The annotation of the CDC20121308 strain identified 26% of CDS into RAST subsystems. We also detected the presence of RT 027 lineage markers such as thyA, cdtA, cdtB and tcdC 18bp-deletion. Moreover, the genome of CDC20121308 had 11 genes devoted to resistance to toxic compounds, antibiotics (e.g. Tetracycline (Tet) and Vancomycin (Van)) and disinfecting agents as predicted using CARD. C. difficile CDC20121308 resistance to Van and Tet was confirmed by broth microdilution assay. Crystal violet staining demonstrated biofilm formation, which could be associated with antibiotic resistance and pathogenicity. Additionally, we observed a spreading diffuse growth in soft agar tubes, suggesting a motile phenotype. Lastly, a genomic region containing Type 4 Secretory System components such as virD4, virB4, and virB6 was identified. In conclusion, our results allowed a genomic and functional characterization of the BI/NAP1/027 C. difficile CDC20121308 strain. We demonstrated the presence of several genes associated with pathogenesis that were validated by experimental assays. This study provides additional data for the use of this highly virulence commercial strain of epidemiological relevance in research works involving in vitro and in vivo approaches.