Project description:Objectives: Colistin remains a last-line treatment for multidrug-resistant Acinetobacter baumannii and combined use of colistin and carbapenems has shown synergistic effects against multidrug-resistant strains. In order to understand the bacterial responses to these antibiotics we analysed the transcriptome of A. baumannii following exposure to each.
Project description:Many clinically relevant bacterial pathogens are encapsulated, as exemplified by Salmonella enterica serovar Typhi. S. Typhi, the causative agent of the life-threatening systemic disease enteric fever, expresses Vi as the outermost surface glycan that protects the bacteria from host immune responses. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) S. Typhi strains, as well as Vi variants, are widespread globally. Our WGS analyses indicate that almost all S. Typhi clinical isolates are susceptible to rifamycins and azithromycin. Rifampin, even at sub-MIC levels, eliminates the protective capsule Vi, a process referred to as ‘decapsulation’, thereby enhancing bacterial clearance. Antibiotic-mediated decapsulation of S. Typhi appears specific to rifamycins, since azithromycin does not decapsulate S. Typhi. Rifampin mediated decapsulation occurs at the transcriptional level, where both high AT content and specific RpoB residues play a crucial role. Rifampin also effectively decapsulates Vi variants, which accounts for 1 in 5 S. Typhi isolates at the global level. A mechanistic explanation for rifampin mediated decapsulation of S. Typhi appears to be applicable to other encapsulated pathogens, including S. Paratyphi C.
Project description:The leaf surface, known as the phylloplane, represents the initial point of contact for plants in their interaction with the aboveground environment. Although prior research has assessed how leaves respond to external pH variations, particularly in the context of acid rain, there remains a limited understanding of the molecular mechanisms through which plants detect, respond to, and mitigate cellular damage. To look at plant responses to external pH changes, we measured the phylloplane pH for five species with variable phylloplane pH that ranged in the dry control. Moreover, we investigated the phylloplane pH in response to three pH treatments (pH 6.5, 4, and 2) and found that plants can modify their phylloplane pH, and this buffering ability is species-specific. Among the species analyzed, only Gossypium displayed a strong buffering ability. For treatments where leaves were exposed to either pH 6.5 or pH 4, Gossypium alkalinized the phylloplane pH slightly higher than the dry control pH. Remarkably, when leaves were exposed to pH 2, Gossypium was able to buffer the pH to 6 within five minutes. Furthermore, our transcriptional analysis indicated that the responses to external pH changes varied among species, highlighting differentially expressed genes associated with calcium (Ca2+) signaling pathways, as well as Ca2+ and H+-ATPases pumps. These findings also suggest that pH stress negatively impacts photosynthesis, and that both wetness and moderate pH shifts may trigger additional abiotic and biotic stress signaling pathways.
Project description:The global prevalence of multidrug-resistant bacteria represents an urgent public health challenge, emphasising the critical need for novel antimicrobial agents. Multidrug-resistant (MDR) Acinetobacter baumannii, a nosocomial pathogen of critical global concern owing to its capacity to acquire and disseminate antimicrobial resistance, was employed as a bacterial model to investigate the antimicrobial potential of natural products derived from Caesalpinia pulcherrima (L.) Sw. (Fabaceae).
Project description:Biofilm lifestyle is critical for bacterial pathogens to colonize and protect themselves from host immunity and antimicrobial chemicals in plants and animals. The formation and regulation mechanism of phytobacterial biofilm are still obscure. Here, we found that Ralstonia solanacearum Resistance to ultraviolet C (RuvC) is highly abundant in biofilm and positively regulates pathogenicity by governing systemic movement in tomato xylem. RuvC protein accumulates at the later stage of biofilm and specifically targets the Holliday junction (HJ) like structures to disrupt biofilm extracellular DNA (eDNA) lattice, thus facilitating biofilm dispersal. Recombinant RuvC protein can resolve extracellular HJ prevent bacterial biofilm formation. Heterologous expression of R. solanacearum or Xanthomonas oryzae pv. oryzae RuvC with plant secretion signal in tomato or rice confers resistance to bacterial wilt or bacterial blight disease, respectively. Plant chloroplast localized HJ resolvase monokaryotic chloroplast 1 (MOC1) which is structural similar to bacterial RuvC shows a strong inhibit effect on bacterial biofilm formation. Re-localization of SlMOC1 to apoplast in tomato roots leads to increase resistance to bacterial wilt. Our novel finding reveals a critical pathogenesis mechanism of R. solanacearum and provides an efficient biotechnology strategy to improve plant resistance to bacteria vascular disease.
Project description:Imipenem-relebactam (Imi/Rel) is a β-lactam/β-lactamase inhibitor combination that is used for the treatment of multidrug-resistant Pseudomonas aeruginosa infections. We previously reported that treatment-emergent resistance is associated with mutations in AmpC, MexAB-OprM and MexEF-OprN efflux operons; however the impact of these mutations on bacterial gene expression have not been explored extensively, particularly among patients treated with Imi/Rel. To determine the effect of treatment-emergent Imi/Rel resistance on P. aeruginosa global transcription, we performed RNA sequencing on 12 paired P. aeruginosa clinical isolates collected from six patients before and after Imi/Rel treatment. Transcriptional responses varied substantially across patients, with no conserved changes in gene expression identified across all six patients. Three isolate pairs showed significant upregulation of previously characterized Imi/Rel resistance-associated genes in the treatment-emergent resistant isolate, while two resistant isolates displayed significant downregulation of ampC. Comparisons of the top 10 differentially regulated genes in the resistant isolate from each patient revealed only one gene that was shared among all six patients. Gene set enrichment analysis using Clusters of Orthologous Group (COGs) suggested that Imi/Rel exposure may impact transcription of genes involved in translation and metabolism , and that these changes are highly variable between patients and isolates. Overall, the transcriptional response of clinical P. aeruginosa to Imi/Rel exposure appears to be highly diverse and likely dependent on the genetic background of the infecting P. aeruginosa strain.
Project description:Candida tropicalis is a leading cause of invasive candidiasis in the Asia-Pacific region with reported crude mortality rates exceeding 50%. The rising prevalence of azole-resistant strains presents a significant clinical challenge. We analyzed 1,016 C. tropicalis clinical isolates collected over nine years from 27 hospitals across North India. Fluconazole resistance was detected in 5.1% (n = 52) of isolates, with cross-resistance observed to voriconazole in 55.7% and itraconazole in 44.2% of isolates. Multilocus sequence typing (MLST) analysis of global 1,630 isolates including 208 Indian and whole-genome sequencing of 716 global isolates (139 Indian) confirmed the clonal emergence and persistence of azole-resistant MLST clade 4 strains in Indian hospitals. Phylogenomic analyses identified that Indian azole-resistant lineage was closely related to azole-resistant isolates from mainland China and Taiwan. The underlying mechanism of resistance involved hotspot mutations (Y132F) in the ERG11 gene along with its duplication, overexpression, and twofold high ergosterol content. Comparative transcriptomics of two clinical isolates exhibiting >512 fold difference in fluconazole susceptibility identified upregulation of virulence-associated genes, ALS7 gene (eightfold), SAP7 and SAP9 (1.6- and 2-fold, respectively) in azole-resistant isolate. Furthermore, azole-resistant isolates showed robust biofilm-associated metabolic activity (twofold), reduced β-glucan exposure, and greater survival in both neutrophil and macrophage killing assays. Notably, azole-resistant lineage exhibits several traits associated with adhesion and immune evasion that could possibly enable its spread in healthcare settings and signals the beginning of a greater spread of this clone. The urgent need for continuous genomic surveillance and antifungal stewardship is warranted to mitigate the spread of multidrug-resistant C. tropicalis.
Project description:This study evaluated the transcriptomic profiles of Arabidopsis thaliana (Col-0) plants grown along bacterial isolates whose interactions induce root morhology changes in the plant
Project description:Polymyxin B is considered as a last-resort antibiotic for multidrug-resistant or extensively drug-resistant gram-negative bacterial infections. Addressing Salmonella resistance to polymyxin B is crucial for global public health. In this study, transcriptomic detection and analysis were used to clarify the mechanisms by which CpxA-deleted S.typhimurium is involved in resistance to polymyxin B stress, which may be related to processes such as increased assembly of bacterial flagella.