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The exchange of genes between bacterial chromosome and plasmid(s) and their integration into integrons are mainly responsible for acquisition and dissemination of antibiotic resistance. We investigated the role of integrons and their underlying molecular mechanisms leading to development of adaptability in E. coli and eventual resistance to antimicrobials. Escherichia coli isolates (n = 120); including 40 diarrheagenic isolates, an even number of isolates from cases other than diarrhea, and equal number of isolates from healthy children recovered from fresh stool samples were used for identification of integron genes and gene cassettes. The association of integrons with antibiotic resistance was assayed before phylogenetic analysis. DNA sequence analysis revealed class 1 and 2 integrons in 55.83% and 21.66% isolates, respectively. The integron presence was found significantly associated with the probability of antibiotic resistance in E. coli; the association being highest with class 1 integron. Modelling and molecular docking along with molecular dynamics simulation analyses found ceftriaxone and amoxicillin as potential inhibitors of dihydrofolate reductase (DHFR). The class 1 integrons of these pathogenic isolates can serve as prospective therapeutic targets using specific silencing strategies and combinational antimicrobial therapy. The findings may be useful for the development of a potent and versatile drug for DHFR inhibition.

Quorum sensing (QS) is a complex bacterial intercellular communication system. It is mediated by molecules called auto-inducers (AIs) and allows coordinated responses to a variety of environmental signals by inducing alterations in gene expression. Communication through QS can tremendously stimulate the pathogenicity and virulence via multiple mechanisms in pathogenic bacteria. The present review explores the major types of multitudinous QS systems known in Gram-positive and Gram-negative bacteria and their roles in bacterial pathogenesis and drug resistance. Because bacterial resistance to antibiotics is increasingly becoming a significant clinical challenge to human health; alternate strategies to combat drug resistance are warranted. Targeting bacterial pathogenicity by interruptions in QS using natural QS inhibitors and synthetic quorum-quenching analogs are being increasingly considered for development of next generation antimicrobials. The review highlights the recent advancements in discovery of promising new QS modulators and their efficiency in controlling infections caused by multidrug-resistant bacterial pathogens.

Background Human Cytomegalovirus (CMV), because of its ability to extensively manipulate host immunity during active infection, has been suggested to be involved in autoimmunity. However, its influence on T-cells and cytokines in systemic autoimmune diseases like systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) is indistinct. Methods We investigated the in-vitro response of T lymphocytes from SLE and SSc patients to CMV antigen. Functional activity of T lymphocytes was determined by estimating Th1 (IL-2 and IFN-γ) and Th2 (IL-4 and IL-10) cytokines. Results We observed that CMV antigen stimulation in-vitro resulted in significant increase in CD4:CD8 T-cell ratio in peripheral blood mononuclear cells (PBMCs) from SLE and SSc patients; response dominated by CD4+ than CD8+ memory T-cells. SSc T-cell response was differentiated by aberrant increase in CD4+CD25+ T-cells. CMV antigen caused elevation in IL-4 and IFN-γ production in both patient PBMCs, whereas IL-2 was also raised in SLE PBMCs. The development of large pool of memory T-cells and overproduction of IFN-γ may result in flare-up of autoimmunity in these patients. Conclusion Our study provides an insight into the immunopathological potential of CMV-reactive immune cells to develop new potential strategies for targeted therapeutic intervention.

Efforts to develop preventatives against HIV infection through sexual route have identified, among many, algal lectins as the potent molecules for scaffolding HIV entry inhibition. Algal lectin scytovirin (SVN) from Scytonema varium, a cyanobacterium, has anti-HIV effects with the potential for use in sculpting HIV neutralization. We created a recombinant strain of human vaginal L. plantarum for extracellular expression of recombinant (r)SVN. The rSVN protein containing culture supernatant was analyzed for its binding with HIV-1 gp160, and for inhibiting infection with primary R5 and X4 HIV-1 strains in TZM-bl cells. The rSVN protein extant in recombinant L. plantarum culture supernatant binds to HIV-1 gp160 and reduces the HIV-induced cytopathic effect to nearly 56.67% and 86.47% in R5 and X4 HIV-1 infected TZM-bl cells, respectively. The fortified L. plantarum may be explored for its use as a live virucide in vaginal mucosa of high risk women to prevent HIV entry.