Vaccines and monoclonal antibodies to prevent healthcare-associated bacterial infections

Clinical Microbiology Reviews, Journal Year: 2024, Volume and Issue: 37(3)

Published: Aug. 9, 2024

SUMMARY Healthcare-associated infections (HAIs) represent a burden for public health with high prevalence and death rates associated them. Pathogens potential antimicrobial resistance, such as ESKAPE pathogens ( E nterococcus faecium, S taphylococcus aureus, K lebsiella pneumoniae, A cinetobacter baumannii, P seudomonas aeruginosa, nterobacter species ) Clostridioides difficile , are responsible most HAIs. Despite the implementation of infection prevention control intervention, globally, HAIs is stable they mainly due to endogenous pathogens. It undeniable that complementary measures, prophylactic approaches by active or passive immunization needed. Specific groups at-risk (elderly people, chronic condition immunocompromised) also healthcare workers key targets. Medical procedures specific interventions known be at risk HAIs, in addition hospital environmental exposure. Vaccines monoclonal antibodies can seen attractive preventive In this review, we present an overview vaccines clinical development major bacterial Based on current state knowledge, look challenges future perspectives improve these means.

Language: Английский

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E. Coli cytotoxic necrotizing factor-1 promotes colorectal carcinogenesis by causing oxidative stress, DNA damage and intestinal permeability alteration

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Jan. 29, 2025

Abstract Background Bacterial toxins are emerging as promising hallmarks of colorectal cancer (CRC) pathogenesis. In particular, Cytotoxic Necrotizing Factor 1 (CNF1) from E. coli deserves special consideration due to the significantly higher prevalence this toxin gene in CRC patients with respect healthy subjects, and numerous tumor-promoting effects that have been ascribed vitro. Despite evidence, a definitive causal link between CNF1 was missing. Here we investigated whether plays an active role onset by analyzing pro-carcinogenic key specifically induced vitro vivo. Methods Viability assays, confocal microscopy γH2AX 53BP1 molecules cytogenetic analysis were carried out assess CNF1-induced genotoxicity on non-neoplastic intestinal epithelial cells. Caco-2 monolayers 3D spheroids used evaluate permeability alterations CNF1, either presence or absence inflammation. vivo, inflammatory bowel disease (IBD) model exploited carcinogenic potential CNF1. Immunohistochemistry immunofluorescence stainings formalin-fixed paraffin-embedded (FFPE) colon tissue well fecal microbiota composition 16 S rRNA sequencing. Results induces release reactive oxidizing species chromosomal instability addition, modifies directly altering tight junctions’ distribution 2D monolayers, hindering differentiation irregular arrangement these junctions. repeated intrarectal administration formation dysplastic aberrant crypt foci (ACF), produces adenomas IBD model. These accompanied increased neutrophilic infiltration colonic tissue, mixed pro-inflammatory anti-inflammatory cytokine milieu, pro-tumoral modulation microbiota. Conclusions Taken together, our results support hypothesis carcinogenesis. Altogether, findings not only add new knowledge contribution bacterial CRC, but also pave way implementation current screening programs preventive strategies.

Language: Английский

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Modular Combinatorial DNA Assembly of Group B Streptococcus Capsular Polysaccharide Biosynthesis Pathways to Expediate the Production of Novel Glycoconjugate Vaccines

Vaccines, Journal Year: 2025, Volume and Issue: 13(3), P. 279 - 279

Published: March 6, 2025

Background/objectives: Streptococcus agalactiae (or Group B Streptococcus, GBS) is a major cause of neonatal meningitis globally. There are 10 serotypes GBS, which distinguished by their capsular polysaccharide (CPS) structure, with Ia, Ib, II, III, IV and V responsible for up to 99% infections. Currently, there no licensed vaccines against GBS. The most developed candidates glycoconjugate vaccines, can be highly effective but also expensive produce existing approaches unaffordable many parts the world. Biosynthesis recombinant glycans glycoconjugates in tractable strains bacteria offers low-cost alternative approach current chemical conjugation methods. Methods: In this study, we apply combinatorial hierarchical DNA assembly heterologous biosynthesis GBS CPSs E. coli. Each gene was removed from its native regulation, paired synthetic regulatory elements rebuilt bottom generate libraries reconstituted pathways. These pathways were screened glycan using serotype-specific antisera. Results: We identified several configurations that successfully biosynthesised CPSs. Furthermore, exploited conserved nature CPS loci flexibility modular constructing hybrid minimal pool glycosyltransferase genes. show transferase genes homologous function used interchangeably between pathways, obviating need clone complete locus each new assembly. Conclusions: conclusion, report first demonstration coli, key milestone towards development multivalent vaccines.

Language: Английский

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Healthcare-Associated Infections: The Role of Microbial and Environmental Factors in Infection Control—A Narrative Review

Infectious Diseases and Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Language: Английский

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