This study reports the genomic insights into a Streptococcus pneumoniae serotype 17F isolate in Malaysia (IMRCC/SS430/25), collected from an adult patient with aspiration pneumonia in 2025. Phenotypic identification revealed characteristic alpha-haemolytic colonies and optochin susceptibility. Species identity as S. pneumoniae was further verified by bile solubility testing and the 17F serotype was confirmed using the Quellung reaction. The isolate was subjected to whole-genome sequencing using the Oxford Nanopore platform. The assembly yielded a highly accurate, single circular contig of 2,065,967 bp with 100% completeness and 48× coverage. In silico typing assigned the genome to ST2355 within the globally disseminated GPSC10 cluster. Antimicrobial susceptibility testing demonstrated resistance to erythromycin, azithromycin, clindamycin, and tetracycline. This phenotypic profile was concordant with genomic screening which identified the ermB and tetM_8 genes responsible for macrolide-lincosamide-streptogramin B (MLSB) and tetracycline resistance respectively. The penicillin-binding protein allelic profile (pbp1a: 79, pbp2b: 26, pbp2x: 194) predicted uniform susceptibility to beta-lactam antibiotics shown by phenotypic testing of amoxicillin-clavulanate and penicillin. Phylogenomic characterization identified the Malaysian isolate within the predominant global ST2355 clade of GPSC10, clustering alongside isolates from Nepal, the United Kingdom, Bangladesh, and the United States. This study demonstrates the utility of combining routine clinical microbiology with high-resolution genomic surveillance to resolve lineage relationship, reveal underlying resistance mechanisms, and confirm genotype-phenotype concordance.

Multidrug resistant tuberculosis (MDR-TB) poses a serious global health concern. The development of drug-resistant mycobacterial strains is likely influenced by efflux transporters. In this study we created a deletion mutant of MSMEG_3118, a hypothetical efflux pump protein in Mycobacterium smegmatis, and characterized the mutant. It is shown that MSMEG_3118 acts as an efflux pump, and its deletion results in enhanced accumulation of the ethidium bromide. The MSMEG_3118 deletion mutant exhibited noticeable changes in colony morphology, slower growth rates, and reduced biofilm formation, indicating a larger role of this protein in mycobacterial physiology. Lipids profile showed elevated levels of menaquinone in the mutant. Interestingly, the mutant showed increased sensitivity to clofazimine and the proton motive force inhibitor CCCP but rendered higher resistance to several first- and second-line anti-tubercular drugs, such as rifampicin, isoniazid, streptomycin, vancomycin and erythromycin. All the changes in the mutant phenotypes were duly restored in the complemented mutant strain, suggesting a larger role of this protein in addition to an efflux pump transporter. Summarily, these results highlight a complex regulatory network that contributes to the multidrug resistance in mycobacteria.

Ribosome stalling is a major problem in all domains of life. When a ribosome stalls, trailing ribosomes may catch up to and collide with the stalled ribosome, depleting protein synthesis capacity. Here, we describe a novel pathway used by Gram-positive bacteria to rescue ribosome collisions. We used the ATPase defective ABCF protein YdiF(EQ 2 ) to induce ribosome stalling and collisions in Bacillus subtilis . Ribosome profiling (Ribo-seq) of YdiF(EQ 2 )-expressing cells revealed that collided ribosomes are enriched for tmRNA, a functional RNA involved in trans -translation. We confirmed that tmRNA tagging activity is globally increased upon expression of any ATPase defective ABCF as well as in cells treated with the collision-inducing antibiotic erythromycin, suggesting this is a generalizable mechanism to rescue stalled and collided ribosomes. The global increase in tmRNA tagging that occurred in response to both erythromycin and YdiF(EQ2) induced collisions was dependent on the Rae1 endonuclease. Loss of trans -translation in cells experiencing widespread ribosome collisions leads to a severe fitness defect, consistent with the importance of this pathway in rescuing ribosomes stalled on truncated mRNAs that result from ribosome collisions. Altogether, our work supports a model in which Rae1 cleaves mRNA on collided ribosomes, thereby generating a truncated mRNA substrate for trans -translation and leading to rescue and recycling of the collided ribosomes. We term this mechanism C ollision- A ssociated R ae1-induced trans- Translation (CART). CART broadens the repertoire of tools that bacteria use to manage ribosome collisions.

Acne vulgaris is a highly prevalent chronic inflammatory disorder of the pilosebaceous unit that affects the majority of adolescents and young adults. Its pathogenesis is multifactorial and is driven largely by hormonal dysregulation, which promotes excess sebum production and follicular hyperkeratinisation, resulting in pore occlusion and the characteristic inflammatory lesions accompanied by swelling and erythema. Acne is caused by Cutibacterium acnes, which colonizes and activates acquired and innate immune responses. Acne is also produced owing to stimulation of the IGF-1 factor, disturbance of the omega-3 and omega-6 cycles, suppression of FoxO1, and activation of mTORC1, which assists in boosting sebum production. Proven treatments target these mechanisms by utilizing systemic and topical drug-delivery systems. Topical retinoids, which have antiinflammatory and anti-acne properties, such as azelaic acid, benzoyl peroxide, salicylic acid, dapsone, and topical or oral antibiotics, are used to treat acne. However, these formulations have limitations, including the need for prolonged treatment, persistent skin irritation, and the development of antibiotic resistance. To overcome these limitations, novel approaches have been utilized, including AI, nano-based formulations, nanoemulsions, semi-synthetic formulations, and herbal formulations. Recent improvements in acne therapy have focused on enhancing effectiveness and safety. The goal of recent developments in acne therapy is to improve treatment efficacy and safety. New drug delivery systems incorporating nanotechnology improve targeting of damaged areas and reduce side effects.

Tapinarof is an aryl hydrocarbon receptor agonist approved for the treatment of atopic dermatitis (AD) and psoriasis. While common adverse events include headache and folliculitis, comedones and perifollicular hyperpigmentation are under-recognized. Here, we report eight patients with AD or psoriasis who developed comedones and/or perifollicular hyperpigmentation during therapy. Lesions developed primarily at application sites; however, in one patient, lesions occurred at a distant site. Lesions appeared on the face in six patients, the legs in one and the arms in one. Time of onset ranged from 1 to 8 months after initiation of tapinarof therapy. Tapinarof was discontinued in all cases. Three patients were treated with topical adapalene/benzoyl peroxide, with partial improvement in one and minimal improvement in two. One patient showed gradual improvement without additional treatment, whereas the remaining five showed no or minimal improvement during follow-up. Our cases provide important information on under-recognized adverse events during tapinarof therapy.

Azithromycin (AZM) is a second generation macrolide, a semi-synthetic derivative of erythromycin. AZM accumulates extensively in cells and tissues, making the evaluation of potential off-target effects relevant when cellular exposure is prolonged or elevated. This study characterized the in vitro genotoxic, cytostatic, metabolic, and apoptotic effects of AZM in primary human peripheral blood lymphocytes (PBLs) and HepG2 cells. PBL cultures from four healthy donors were exposed to 1.25-5.0 μg/mL AZM for 48 h and assessed using chromosome aberration (CA), micronucleus (MN), mitotic index (MI), and cytokinesis-block proliferation index (CBPI) analyses. HepG2 cells were evaluated using the MTT reduction assay after exposure to 0.312-40 μg/mL AZM for 24-72 h and by Annexin V-APC/7-AAD flow cytometry after 48 h. AZM increased chromosomal aberration and micronucleus frequencies and reduced MI and CBPI in PBLs. In HepG2 cells, AZM reduced MTT-derived metabolic activity in a concentration- and time-dependent manner (48-h IC50: 13.64 μg/mL) and increased apoptotic cell populations, while necrosis remained limited. These findings demonstrate concentration-dependent in vitro toxicological effects in both models.

Antibiotic residues in receiving water bodies of densely populated urban areas have attracted widespread concern. In this study, 35 antibiotics, including tetracyclines, macrolides, sulfonamides, and quinolones, were identified in the Beiyun River system of Beijing, a megacity in China. The spatial distribution patterns and ecological risks related to the target antibiotics in different surface water types were investigated, while their main sources were quantitatively identified using principal component analysis-multiple linear regression (PCA-MLR). The results indicated that all 35 antibiotics occurred at varying levels, with trimethoprim, chlortetracycline, and sulfamethoxazole showing 100% detection frequencies. The total concentrations of individual antibiotics varied between 2.8 ng/L (lomefloxacin) and 1235.8 ng/L (erythromycin). Spatially, antibiotic concentrations followed the order of midstream > downstream > upstream, and levels in tributaries were, in general, higher compared with the main flow, indicating that the mainstream was strongly influenced by tributary inflows. Multiple-level ecological risk assessment indicated that the overall ecological risks posed by antibiotics within the Beiyun River system remained at acceptable levels. However, tetracyclines showed relatively high risk quotients (RQ), and clarithromycin exhibited low risks to certain aquatic species. The PCA-MLR model identified 6 pollution sources and one unknown source. Among these, mixed pollution source inputs (explaining 35.4% of variance) and wastewater treatment plants' discharges (explaining 31.1% of variance) were the primary sources of antibiotics in the surface water of the Beiyun River system. The former contributed most significantly to difloxacin (72.1%) and ciprofloxacin (71.4%), while the latter contributed substantially to sulfacetamide (74.8%), sulfachloropyridazine (73.9%), sulfadimethoxine (73.3%), and sulfadiazine (70.9%). These findings provide valuable insights for antibiotic pollution prevention and management of the risks to ecosystems in urban river systems.

Eczema molluscatum refers to widespread molluscum contagiosum (MC) infection occurring in patients with atopic dermatitis (AD), a setting in which impaired skin barrier function and immune dysregulation both promote viral spread. We report the case of a 29-year-old man with longstanding, treatment-refractory AD who was well controlled on upadacitinib, a selective Janus kinase 1 (JAK1) inhibitor, and methotrexate when he developed multiple pink, dome-shaped papules with central umbilication across the cheeks and forehead over a six-month period. The lesions were unresponsive to topical clindamycin-benzoyl peroxide gel. The differential diagnosis included eczema coxsackium, eczema herpeticum, eruptive syringomas, and a refractory JAK inhibitor-associated acneiform eruption, but the absence of pain, systemic symptoms, vesiculation, and follicular morphology supported a diagnosis of eczema molluscatum. The patient was treated with cryotherapy for each lesion, with marked improvement at one-month follow-up. AD itself is a recognized risk factor for MC, reflecting the disease's inherent Th2-skewed, barrier-disrupted immune environment. However, this case raises the possibility that systemic immunosuppression with JAK1 inhibitors, particularly in combination with methotrexate, may further impair type I interferon-mediated antiviral defense and compound susceptibility to MC in patients with AD. Nonetheless, clinicians should maintain a high index of suspicion for eczema molluscatum in patients with AD on JAK inhibitor therapy who develop new facial papules, as these lesions are readily mistaken for a JAK inhibitor-associated acneiform eruption, potentially delaying appropriate treatment.