Streptococcus pneumoniae (pneumococcus) is a major human pathogen producing structurally diverse capsular polysaccharides. Widespread use of highly successful pneumococcal conjugate vaccines (PCVs) targeting pneumococcal capsules has greatly reduced infections by the vaccine types but increased infections by nonvaccine serotypes. Herein, we report a new and the 100th capsule type, named serotype 10D, by determining its unique chemical structure and biosynthetic roles of all capsule synthesis locus (cps) genes. The name 10D reflects its serologic cross-reaction with serotype 10A and appearance of cross-opsonic antibodies in response to immunization with 10A polysaccharide in a 23-valent pneumococcal vaccine. Genetic analysis showed that 10D cps has three large regions syntenic to and highly homologous with cps loci from serotype 6C, serotype 39, and an oral streptococcus strain (S. mitis SK145). The 10D cps region syntenic to SK145 is about 6 kb and has a short gene fragment of wciNα at the 5′ end. The presence of this nonfunctional wciNα fragment provides compelling evidence for a recent interspecies genetic transfer from oral streptococcus to pneumococcus. Since oral streptococci have a large repertoire of cps loci, widespread PCV usage could facilitate the appearance of novel serotypes through interspecies recombination.
IMPORTANCE The polysaccharide capsule is essential for the pathogenicity of pneumococcus, which is responsible for millions of deaths worldwide each year. Currently available pneumococcal vaccines are designed to elicit antibodies to the capsule polysaccharides of the pneumococcal isolates commonly causing diseases, and the antibodies provide protection only against the pneumococcus expressing the vaccine-targeted capsules. Since pneumococci can produce different capsule polysaccharides and therefore reduce vaccine effectiveness, it is important to track the appearance of novel pneumococcal capsule types and how these new capsules are created. Herein, we describe a new and the 100th pneumococcal capsule type with unique chemical and serological properties. The capsule type was named 10D for its serologic similarity to 10A. Genetic studies provide strong evidence that pneumococcus created 10D capsule polysaccharide by capturing a large genetic fragment from an oral streptococcus. Such interspecies genetic exchanges could greatly increase diversity of pneumococcal capsules and complicate serotype shifts.
Pneumococcal capsules are important in pneumococcal pathogenesis and vaccine development. Though conjugate vaccines have brought about a significant reduction in invasive pneumococcal disease (IPD) caused by vaccine serotypes, the relative serotype prevalence has shifted with dramatic emergence of serotype 24F in some countries. Herein, we describe fourteen isolates (thirteen IPD and one non-IPD) expressing a new capsule type, 24C, which resembles 24F but has a novel serological profile. We also describe the antigenic, biochemical, and genetic bases of 24F and 24C and the related serotypes 24A and 24B. Structural studies show that 24B, 24C, and 24F have identical polysaccharide backbones [β-Rib
f-
(1→4)-α-Rha
p
-(1→3)-β-Glc
p
NAc-(1→4)-β-Rha
p
-(1→4)-β-Glc
p
] but with different side chains: 24F has arabinitol-phosphate, and 24B has ribitol-phosphate. 24C has a mixture of 24F and 24B repeating units, with ratio of ribitol to arabinitol being strain-dependent. In contrast, 24A capsule has a backbone without β-Rib
f
but with arabinitol-phosphate and phosphocholine side chains. These structures indicate that factor-sera 24d and 24e respectively recognize arabinitol and ribitol, which explains the serology of serogroup 24, including those of 24C. The structures can be genetically described by the bi-specificity of
wcxG
, capable of transferring arabinitol or ribitol when arabinitol is limiting. Arabinitol is likely not produced in 24B but is produced in reduced amounts in 24C due to various mutations in
abpA
or
abpB
genes. Our findings demonstrate how pneumococci modulate their capsule structure and immunologic properties with small genetic changes, thereby evading host immune responses. Our findings also suggest a potential for new capsule types within serogroup 24.
Background: The increasing reports on multidrug resistant Escherichia coli has become a potential threat to global health. Here, we present a cross-sectional study to characterize extended spectrum β-lactamase, AmpC β-lactamase and metallo β-lactamase producing E. coli isolated from different human clinical samples.Methods: A total of 300 clinical Gram negative bacterial isolates were collected and re-characterized for the identification of E. coli following standard microbiological techniques. The antimicrobial susceptibility of E. coli isolates was initially screened by Kirby-Bauer disk diffusion and MIC methods. The resistant isolates were confirmed to be ESBL, AmpC and MBL producers by their respective phenotypic confirmatory tests of combined disc method.Results: We identified 203 (68%) E. coli and 97 (32%) Non-E. coli isolates. The highest recovery of E. coli was from urine samples 72 (35%). Combined disc method using ceftazidime/ceftazidime+clavulanic acid and cefotaxime/cefotaxime+clavulanic acid confirmed 156 (79%) and 144 (73%) E. coli as ESBL producers, respectively. Thirty-four (34%) and 16 (27%) resistant E. coli isolates were confirmed to be AmpC and MBL producers, likewise.Conclusions: Increased prevalence of ESBL, AmpC and MBL producing E. coli were observed. Beta-lactamase mediated resistance appears to be prime mechanism in the multidrug resistant E. coli. Thus, early detection of beta lactamase producing E. coli is necessary to avoid treatment failure and prevent the spread of MDR.
While there was no difference in acquisition of VT nasopharyngeal carriage of pneumococcus in CLH and HUC after one dose of PCV13, earlier access to ART may impact response to PCV13 in CLH.
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