Several interconnected human, animal and environmental habitats can contribute to the emergence, evolution and spread of antibiotic resistance, and the health of these contiguous habitats (the focus of the One Health approach) may represent a risk to human health. Additionally, the expansion of resistant clones and antibiotic resistance determinants among human-associated, animal-associated and environmental microbiomes have the potential to alter bacterial population genetics at local and global levels, thereby modifying the structure, and eventually the productivity, of microbiomes where antibiotic-resistant bacteria can expand. Conversely, any change in these habitats (including pollution by antibiotics or by antibiotic-resistant organisms) may influence the structures of their associated bacterial populations, which might affect the spread of antibiotic resistance to, and among, the above-mentioned microbiomes. Besides local transmission among connected habitats-the focus of studies under the One Health concept-the transmission of resistant microorganisms might occur on a broader (even worldwide) scale, requiring coordinated Global Health actions. This Review provides updated information on the elements involved in the evolution and spread of antibiotic resistance at local and global levels, and proposes studies to be performed and strategies to be followed that may help reduce the burden of antibiotic resistance as well as its impact on human and planetary health.

Defining and combating antibiotic resistance from One Health and Global Health perspectives

Elizabethkingia anophelis is an emerging human pathogen causing neonatal meningitis, catheter-associated infections and nosocomial outbreaks with high mortality rates. Besides, they are resistant t...

Proteome-wide screening for designing a multi-epitope vaccine against emerging pathogen Elizabethkingia anophelis using immunoinformatic approaches.

Vaccinomics to design a novel single chimeric subunit vaccine for broad-spectrum immunological applications targeting nosocomial Enterobacteriaceae pathogens.

Overcoming multi drug resistance is one of the crucial challenges to control enteric typhoid fever caused by Salmonella typhi and Salmonella paratyphi. Overexpression of efflux pumps predominantly causes drug resistance in microorganisms. Therefore, immunotherapy targeting the various efflux pumps antigens could be a promising strategy to increase the success of vaccines. An immunoinformatic approach was employed to design a Salmonellosis multi-epitope subunit vaccine peptide consisting of linear B-cell and T-cell epitopes of multidrug resistance protein families including ATP Binding Cassette (ABC), major facilitator superfamily (MFS), resistance nodulation cell division (RND), small multidrug resistance (SMR), and multidrug and toxin extrusion (MATE). The selected epitopes exhibited conservation in both S. typhi and S. paratyphi and thus could be helpful for cross-protection. Further, the final vaccine construct encompassing the peptides, adjuvants and specific linker sequences showed high immunogenicity, solubility, non-allergenic, nontoxic, and wide population coverage due to strong binding affinity to maximum HLA alleles. The three-dimensional structure was predicted, and validated using various structure validation tools. Additionally, protein-protein docking of the chimeric vaccine construct with the TLR-2 protein and molecular dynamics demonstrated stable and efficient binding. Conclusively, the immunoinformatic study showed that the novel multi epitopic vaccine construct can simulate the both T-cell and B-cell immune responses in typhoidal Salmonella serovars and could potentially be used for prophylactic or therapeutic applications.Communicated by Ramaswamy H. Sarma.

Immunoinformatic approach employing modeling and simulation to design a novel vaccine construct targeting MDR efflux pumps to confer wide protection against typhoidal Salmonella serovars.

Interdisciplinary research focused on biological membranes has revealed them as signaling and trafficking platforms for processes fundamental to life. Biomembranes harbor receptors, ion channels, lipid domains, lipid signals, and scaffolding complexes, which function to maintain cellular growth, metabolism, and homeostasis. Moreover, abnormalities in lipid metabolism attributed to genetic changes among other causes are often associated with diseases such as cancer, arthritis and diabetes. Thus, there is a need to comprehensively understand molecular events occurring within and on membranes as a means of grasping disease etiology and identifying viable targets for drug development. A rapidly expanding field in the last decade has centered on understanding membrane recruitment of peripheral proteins. This class of proteins reversibly interacts with specific lipids in a spatial and temporal fashion in crucial biological processes. Typically, recruitment of peripheral proteins to the different cellular sites is mediated by one or more modular lipid-binding domains through specific lipid recognition. Structural, computational, and experimental studies of these lipid-binding domains have demonstrated how they specifically recognize their cognate lipids and achieve subcellular localization. However, the mechanisms by which these modular domains and their host proteins are recruited to and interact with various cell membranes often vary drastically due to differences in lipid affinity, specificity, penetration as well as protein-protein and intramolecular interactions. As there is still a paucity of predictive data for peripheral protein function, these enzymes are often rigorously studied to characterize their lipid-dependent properties. This review summarizes recent progress in our understanding of how peripheral proteins are recruited to biomembranes and highlights avenues to exploit in drug development targeted at cellular membranes and/or lipid-binding proteins.

Cellular membranes and lipid-binding domains as attractive targets for drug development

In silico epitope identification of unique multidrug resistance proteins from Salmonella Typhi for vaccine development

Investigations of binding mode insight in Salmonella typhi type-III secretion system tip protein (SipD): A molecular docking and MD simulation study

Typhoid fever is an acute illness in humans, caused by Salmonella typhi, a gram-negative bacterium. Outer membrane proteins of S. typhi have strong potential for its use in the development...

In Silico Characterization of B Cell and T Cell Epitopes for Subunit Vaccine Design of Salmonella typhi PgtE: A Molecular Dynamics Simulation Approach.

http://ijlssr.com/currentissue/ProGene%201.0-An%20In%20Silico%20Tool%20for%20Protein-Gene%20Analysis.pdf

Sundarabaalaji Narayanan

Papers

In silico epitope identification of unique multidrug resistance proteins from Salmonella Typhi for vaccine development

Investigations of binding mode insight in Salmonella typhi type-III secretion system tip protein (SipD): A molecular docking and MD simulation study

In Silico Characterization of B Cell and T Cell Epitopes for Subunit Vaccine Design of Salmonella typhi PgtE: A Molecular Dynamics Simulation Approach.

ProGene 1.0-An In Silico Tool for Protein-Gene Analysis

B-cell and T-cell epitope identification with stability analysis of AI-2 import ATP-binding cassette LsrA from S. typhiIn silico approach.