Biology subjects

Skoczynska, A.

Publications and source records attributed to Skoczynska, A..

3 recordsLinked to original sources

bioRxiv2024

Unravelling the Proteomic Landscape of Imipenem Resistance in Pseudomonas aeruginosa: A Comparative Investigation between Clinical and Control Strains

The increasing prevalence of antimicrobial resistance (AMR) poses a significant challenge to global health, particularly with bacterial pathogens such as Pseudomonas aeruginosa, a notorious cause of nosocomial infections. This study focuses on the comparative proteomic analysis of an imipenem-resistant strain of P. aeruginosa, a representative of world epidemic clone ST235, and a wildtype control strain, P. aeruginosa ATCC 27853, in response to varying concentrations of imipenem. Using label-free quantification (LFQ) and gene ontology (GO) enrichment analyses, we identified significant differences in the proteomic responses between the two strains (data available via ProteomeXchange with identifier PXD055744.). The clinical strain exhibited a stable proteomic profile across the imipenem gradient, suggesting pre-established and efficient resistance mechanisms that do not require extensive reconfiguration under antibiotic pressure. In contrast, the control strain showed a broader, more reactive proteomic response, particularly in proteins associated with membrane transport, stress response, and biofilm formation. Notably, uncharacterized proteins were significantly upregulated in the clinical strain, indicating potential novel resistance mechanisms. These findings highlight the distinct strategies employed by the two strains, with the clinical strains stable resistance mechanisms contrasting sharply with the control strains reactive approach. The study underscores the importance of further research into the uncharacterized proteins that may play crucial roles in antibiotic resistance, potentially leading to new therapeutic targets in the fight against AMR. HighlightsO_LIStable resistance mechanisms: The clinical strain of Pseudomonas aeruginosa (ST235) exhibited a stable proteomic profile across varying concentrations of imipenem, indicating pre-established and efficient resistance mechanisms. C_LIO_LIReactive proteomic response: The control strain (P. aeruginosa ATCC 27853) showed a broader and more reactive proteomic response, particularly in proteins related to membrane transport, stress response, and biofilm formation. C_LIO_LIUncharacterized proteins: Significant upregulation of uncharacterized proteins in the clinical strain suggests potential novel resistance mechanisms that warrant further investigation. C_LI

microbiology↗

bioRxiv2019

A novel mosaic tetracycline resistance gene tet(S/M) detected in a multidrug-resistant pneumococcal CC230 lineage that underwent capsular switching in South Africa

SynopsisO_ST_ABSObjectiveC_ST_ABSWe reported a novel tetracycline-resistant gene in Streptococcus pneumoniae and investigated its temporal spread in relation to nationwide clinical interventions.\n\nMethodsWe whole genome sequenced 12,254 pneumococcal isolates from twenty-nine countries on an Illumina HiSeq Sequencer. Serotypes, sequence types and antibiotic resistance were inferred from genomes. Phylogeny was built based on single-nucleotide variants. Temporal changes of spread were reconstructed using a birth-death model.\n\nResultsWe identified tet(S/M) in 131 pneumococcal isolates, 97 (74%) caused invasive pneumococcal diseases among young children (59% HIV-positive, where HIV status was available) in South Africa. A majority of tet(S/M)-positive isolates (129/131) belong to clonal complex (CC)230. A global phylogeny of CC230 (n=389) revealed that tet(S/M)-positive isolates formed a sub-lineage that exhibited multidrug-resistance. Using the genomic data and a birth-death model, we detected an unrecognised outbreak of this sub-lineage in South Africa between 2000 and 2004 with an expected secondary infections (R) of ~2.5. R declined to ~1.0 in 2005 and <1.0 in 2012. The declining epidemic coincided and could be related to the nationwide implementation of anti-retroviral treatment (ART) for HIV-infected individuals in 2004 and PCVs in late 2000s. Capsular switching from vaccine serotype 14 to non-vaccine serotype 23A was observed within the sub-lineage.\n\nConclusionsThe prevalence of tet(S/M) in pneumococci was low and its dissemination was due to an unrecognised outbreak of CC230 in South Africa prior to ART and PCVs. However, capsular switching in this multidrug-resistant sub-lineage highlighted its potential to continue to cause disease in the post-PCV13 era.

microbiology↗

bioRxiv2018

Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci

Streptococcus pneumoniae serotype 3 remains a significant cause of morbidity and mortality worldwide, despite inclusion in the 13-valent pneumococcal conjugate vaccine (PCV13). Serotype 3 increased in carriage since the implementation of PCV13 in the United States, while invasive disease rates remain unchanged. We investigated the persistence of serotype 3 in carriage and disease, through genomic analyses of a global sample of 301 serotype 3 isolates of the Netherlands3-31 (PMEN31) clone CC180, combined with associated patient data and PCV utilization among countries of isolate collection. We assessed phenotypic variation between dominant clades in capsule charge (zeta potential), capsular polysaccharide shedding, and susceptibility to opsonophagocytic killing, which have previously been associated with carriage duration, invasiveness, and vaccine escape. We identify a recent shift in the CC180 population attributed to a lineage termed Clade II, which was estimated by Bayesian coalescent analysis to have first appeared in 1968 [95% HPD: 1939-1989] and increased in prevalence and effective population size thereafter. Clade II isolates are divergent from the pre-PCV13 serotype 3 population in non-capsular antigenic composition, competence, and antibiotic susceptibility, the last resulting from the acquisition of a Tn916-like conjugative transposon. Differences in recombination rates among clades correlated with variations in the ATP-binding subunit of Clp protease as well as amino acid substitutions in the comCDE operon. Opsonophagocytic killing assays elucidated the low observed efficacy of PCV13 against serotype 3. Variation in PCV13 use among sampled countries was not independently correlated with the CC180 population shift; therefore, genotypic and phenotypic differences in protein antigens and, in particular, antibiotic resistance may have contributed to the increase of Clade II. Our analysis emphasizes the need for routine, representative sampling of isolates from disperse geographic regions, including historically under-sampled areas. We also highlight the value of genomics in resolving antigenic and epidemiological variations within a serotype, which may have implications for future vaccine development.\n\nAuthor SummaryStreptococcus pneumoniae is a leading cause of bacterial pneumoniae, meningitis, and otitis media. Despite inclusion in the most recent pneumococcal conjugate vaccine, PCV13, serotype 3 remains epidemiologically important globally. We investigated the persistence of serotype 3 using whole-genome sequencing data form 301 isolates collected among 24 countries from 1993-2014. Through phylogenetic analysis, we identified three distinct lineages within a single clonal complex, CC180, and found one has recently emerged and grown in prevalence. We then compared genomic difference among lineages as well as variations in pneumococcal vaccine use among sampled countries. We found that the recently emerged lineage, termed Clade II, has a higher prevalence of antibiotic resistance compared to other lineages, diverse surface protein antigens, and a higher rate of recombination, a process by which bacteria can uptake and incorporate genetic material from its surroundings. Differences in vaccine use among sampled countries did not appear to be associated with the emergence of Clade II. We highlight the need to routine, representative sampling of bacterial isolates from diverse geographic areas and show the utility of genomic data in resolving epidemiological differences within a pathogen population.

evolutionary biology↗