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PubMed2026

Isolation and Characterization of Lytic Bacteriophages Targeting Clinical Staphylococcus Other Than S. aureus.

Staphylococcus spp., other than S. aureus (SOSA, formerly CoNS), are opportunistic pathogens often linked to biofilm infections on indwelling devices. Their rising antibiotic resistance highlights the need for novel therapies. Bacteriophages are promising due to their specificity and ability to inhibit cell growth and biofilm formation. In this study, lytic phages isolated from swab pools were characterized against six clinical S. epidermidis and S. warneri isolates. Two distinct groups were identified via their host range, transmission electron microscopy, and genome sequencing. Group 1 phage ΘBRJ9 belongs to genus Sepunavirus (Myoviridae), while Group 2 phage ΘBRJ18 belongs to genus Andhravirus (Podoviridae). Both showed rapid adsorption, short latent periods (20 min), and high burst sizes (79 and 60 PFU/cell). They strongly inhibited planktonic SOSA growth at MOI 10, with efficacy comparable to or better than vancomycin, and their genomes lacked lysogeny, virulence, or resistance genes. These phages display a lytic lifestyle and are candidates for targeted SOSA therapies. Future work will assess biofilm efficacy, antibiotic synergies, and in vivo performance.

Antibiotic resistance↗

PubMed2026

Analysis of structure and conservation for supporting functional evaluation of PMS2 missense variants.

Germline defects in mismatch repair (MMR) genes are known to significantly increase the risk of developing certain types of cancers, notably colorectal and endometrial cancers. These conditions are characterized under Lynch syndrome. Accurate diagnosis of this predisposition, along with meaningful predictive testing for family members, necessitates the identification of pathogenic variants. However, classifying small coding genetic variants identified in cancer patients is very challenging, specifically in the case of PMS2 variants, since PMS2 pathogenic variants display a lower penetrance and less severe phenotype and therefore a lower tumor burden in affected families. We have assembled clinical data on four PMS2 missense variants of uncertain significance (VUS) identified in 23 patients (p.(Asp286Gly), p.(Asn335Ser), p.(Ile679Thr) and p.(Arg799Trp)). For these variants, functional testing was performed (RNA splicing, protein stability and catalytic activity). Since many protein ortholog sequences and accurate predictive models from AlphaFold2 are available, we also included a systematic analysis of residue conservation and structural role (ConStruct assessment). Overall, our findings indicate that p.(Asp286Gly) and p.(Arg799Trp) behave similarly to wild-type PMS2 and are thus probably neutral. In contrast, p.(Asn335Ser) and p.(Ile679Thr) conferred defects in protein expression or MMR activity. These could be explained by the relevant roles of these amino acids in MLH1-PMS2-N-terminal dimerization (p.Asn335) and C-terminal dimerization (p.Ile679). Our data thus suggest that p.(Asp286Gly) and p.(Arg799Trp) are benign, while the tumor risk in the other two variants remains to be established. Taken together, we suggest roadmaps for the individualized evaluation of difficult uncertain variants by comprising information from all available sources.

Humans↗