Using Omics Technologies and Systems Biology to Identify Epitope Targets for the Development of Monoclonal Antibodies Against Antibiotic-Resistant Bacteria

Over the past few decades, antimicrobial resistance has emerged as an important threat to public health due to the global dissemination of multidrug-resistant strains from several bacterial species. This worrisome trend, in addition to the paucity of new antibiotics with novel mechanisms of action in the development pipeline, warrants the development of non-antimicrobial approaches to combating infection caused by these isolates. Monoclonal antibodies (mAbs) have emerged as highly effective molecules for the treatment of multiple diseases. However, in spite of the fact that antibodies play an important role in protective immunity against bacteria, only three mAb therapies have been approved for clinical use in the treatment of bacterial infections. In the present review, we briefly outline the therapeutic potential of mAbs in the treatment of bacterial diseases and discuss how their development can be facilitated when assisted by “omics” technologies and interpreted under a systems biology paradigm. Specifically, methods employing large genomic, transcriptomic, structural, and proteomic datasets allow for the rational identification of epitopes. Ideally, these include those that are present in the majority of circulating isolates, highly conserved at the amino acid level, surface-exposed, located on antigens essential for virulence, and expressed during critical stages of infection. Therefore, these knowledge-based approaches can contribute to the identification o...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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Conclusion: Our findings raise potential public health concerns for environmental contamination of MRSA and MRSE in school environments. Surfaces of school environments may potentially provide a source for cross-contamination with these bacteria into the wider community.
Source: International Journal of Environmental Research and Public Health - Category: Environmental Health Authors: Tags: Article Source Type: research
ConclusionsIt is believed that this is the first molecular characterisation of wound infection pathogens from Madagascan patients and the first description of P. rettgeri co-producing CMY-30, OXA-10 and AAC(6’)-Ib-cr4 enzymes. The diversity of the resistance determinants and mobile genetic elements was probably due to extensive horizontal gene transfer events, highlighting the need to conduct further molecular monitoring studies to understand the genomic plasticity of resistant bacteria in Madagascan hospitals.
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
Publication date: Available online 11 January 2020Source: Food ControlAuthor(s): Chujun Ou, Daiqi Shang, Jingxian Yang, Bo Chen, Jiang Chang, Fangning Jin, Chunlei ShiAbstractAntimicrobial resistance has gradually become a serious problem threatening public health and food safety throughout the world. Biofilm is one of the important factors affecting the antimicrobial resistance of bacteria. Staphylococcus aureus usually has strong biofilm formation ability, and it is widely found in animal-based food. The purpose of this study is to determine the prevalence, antimicrobial resistance and biofilm formation of S. aureus in a...
Source: Food Control - Category: Food Science Source Type: research
AbstractAntimicrobial resistance (AMR) is an increasing problem. The prevalence of antimicrobial resistance in general practice patients is expected to be relatively high in Rotterdam, the Dutch city with the largest proportion non-Western immigrants. The aim of this study was to assess the prevalence of antibiotic-resistant uropathogens (Escherichia coli,Klebsiella pneumoniae, andProteus mirabilis) in general practices in Rotterdam, and to find a possible association between the prevalence of antibiotic-resistantE. coli and age, gender, and socioeconomic status (SES). A retrospective analysis was performed of urine sample...
Source: European Journal of Clinical Microbiology and Infectious Diseases - Category: Microbiology Source Type: research
ConclusionsThe percentage of European ICU physicians perceiving AMR as a substantial problem in their ICU is high with variation by sub-region in line with epidemiological studies. The reports of bacteria resistant to almost all available antibiotics and the limited availability of last-line antibiotics in ICUs in the EU/EEA are of concern.
Source: Antimicrobial Resistance and Infection Control - Category: Infectious Diseases Source Type: research
This study aimed to investigate the antimicrobial resistance profile, multidrug resistance (MDR), and molecular characteristics of pathogenic Staphylococcus aureus isolates among hospitalized Vietnamese adults. Two-hundred twenty-three pathogenic S. aureus isolates were collected from hospitals in three regions of Vietnam. The minimum inhibitory concentrations were determined for antibiotic susceptibility of isolates. The molecular characteristics of S. aureus isolates were investigated using analysis of antibiotic-resistant genes, staphylococcal cassette chromosome mec typing, pulsed-field gel electrophoresis, and multilo...
Source: Japanese Journal of Infectious Diseases - Category: Infectious Diseases Authors: Tags: Jpn J Infect Dis Source Type: research
ConclusionsMultiple resistance genes are located in a complex class 1 integron within a 42-kb T. pyogenes genomic island (TGI1), leading TP1 multiple drug resistance. In comparison with SG1 families, TGI1 possesses versatile gene distribution and specific gene context for its upstream and downstream, and it represents a new lineage of genomic resistance islands.
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
ConclusionsThere was a relatively high prevalence of colonisation with MDROs, particularly ESBL-E, but lowC. difficile carriage, with implications for antibiotic prescribing and infection control practice.
Source: Antimicrobial Resistance and Infection Control - Category: Infectious Diseases Source Type: research
Authors: Yu H, Wang Y, Wang X, Guo J, Wang H, Zhang H, Du F Abstract Bacterial resistance to antimicrobial agents, including multidrug resistance, is an increasing problem in the treatment of infectious diseases. The development of resistance-modifying agents represents a potential strategy to alleviate the spread of bacterial resistance to antibiotics. A checkerboard microdilution assay was used to determine the synergy of jatrorrhizine and the antibiotic, norfloxacin (NFX). A bacterial ethidium bromide efflux assay, reverse transcription semi-quantitative polymerase chain reaction analysis and molecular docking s...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
Authors: Bader MS, Loeb M, Leto D, Brooks AA Abstract Urinary tract infections (UTIs) caused by antibiotic- resistant Gram-negative bacteria are a growing concern due to limited treatment options. Knowledge of the common uropathogens in addition to local susceptibility patterns is essential in determining appropriate empiric antibiotic therapy of UTIs. The recommended first-line empiric antibiotic therapy for acute uncomplicated bacterial cystitis in otherwise healthy adult nonpregnant females is a 5-day course of nitrofurantion, a 3-g single dose of fosfomycin tromethamine, or a 5-day course of pevmecillinam. High...
Source: Postgraduate Medicine - Category: Internal Medicine Tags: Postgrad Med Source Type: research
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