Bacteriophage for Mitigation of Multiple Drug Resistant Biofilm Forming Pathogens.

BACKGROUND: Microbial communities encased in exopolymeric substances (EPS) attached to suitable substrate as biofilms show heightened resistance to multiple drugs including antibiotics. One promising control strategy in dealing with the ever mounting problem of antibiotic resistance amongst biofilm forming bacterial pathogens is the use of biological agents. OBJECTIVE: This review focuses on the development of bacteriophages as means of disrupting biofilm forming pathogens and hence mitigation of multiple drug resistant organisms. RESULTS: Bacteriophages are obligatory viral intracellular parasites that can cause lytic infection of their bacterial hosts. Bacteriophage (Phage) therapy is advantageous in being highly host specific, safe and non-toxic to humans and hence environmental friendly. Bacteriophage induced lysis of cells within the biofilm is aided by the production of penetrating enzymes such as endolysins and EPS depolymerases as well quorum sensing inhibitors such as lactonases. CONCLUSION: Phages are a promising alternative therapy for the control of multiple drug resistant (MDR) pathogens. Several phage (indigenous and engineered)/ phage products are currently being patented and developed as commercial biological control agents.

Hexavalent chromium reduction and plant growth promotion by Staphylococcusarlettae strain Cr11.

Cr(VI), a mutagenic and carcinogenic pollutant in industrial effluents, was effectively reduced by an indigenous tannery effluent isolate Staphylococcus arlettae strain Cr11 under aerobic conditions. The isolate could tolerate Cr(VI) up to 2000 and 5000 mg L(-1) in liquid and solid media respectively. S. arlettae Cr11 effectively reduced 98% of 100 mg L(-1) Cr(VI) in 24h. Reduction for initial Cr(VI) concentrations of 500 and 1000 mg L(-1) was 98% and 75%, respectively in 120 h. The isolate was also positive for siderophore, indole acetic acid, ammonia and catalase production, phosphate solubilization and biofilm formation in the presence and absence of Cr(VI). The isolate showed halotolerance (10% NaCl) and cross tolerance to other toxic heavy metals such as Hg(2+), Ni(2+), Cd(2+) and Pb(2+). Bacterial inoculation of Triticum aestivum in controlled petri dish and soil environment showed significant increase in percent germination, root and shoot length as well as dry and wet weight in Cr(VI) treated and untreated samples. This is the first report of simultaneous Cr(VI) reduction and plant growth promotion for a S. arlettae strain.

Homology modeling of phosphoryl thymidine kinase of enterohemorrhagic Escherichia coli OH: 157.

Enterohemorrhagic Escherichia coli (EHEC) are source of emerging infectious disease in India. Escherichia coli O157:H7 is an EHEC strain showing multiple antibiotic resistances and the cause of infantile diarrhea and hemolytic uremic syndrome worldwide. A novel strategy to counteract multiple antibiotic resistant organisms is to design drugs which specifically target metabolic pathways such as thiamine biosynthetic pathways found exclusively in prokaryotes. Homology modeling was used for model building of a terminal thiamine biosynthesis enzyme phosphoryl thymidine kinase (Thi E) using Geno3D, Swiss Model and Modeller. The best model was selected based on overall stereochemical quality. The potential ligand binding sites in the model were identified by CASTp server. The validated theoretical model of the 3D structure of the thiE protein of E. coli O157:H7 was predicted using a thiamine phosphate pyrophosphatase from Pyrococcus furiosus (PDB ID: 1X13_A) as template. The active pockets of ligand binding sites in the enzyme were identified. In this study, phosphoryl thymidine kinase (thi E), a terminal enzyme in the thiamine biosynthesis pathway in the pathogen has been modeled to be used in future as a potential drug target by the design of suitable inhibitors.

Enhanced viral immunoinflammatory lesions in mice lacking IL-23 responses.

Herpes simplex virus (HSV) infection of the cornea culminates in an immunopathological lesion (stromal keratitis--SK) that impairs vision. This report shows that HSV infection results in IL-23 up-regulation, but if this response fails to occur, as was noted in p19-/- mice, the severity of lesions, their incidence and the level of viral induced angiogenesis were significantly increased compared to wild-type (WT) animals (p<0.05). The higher disease severity in p19-/- mice appeared to be the consequence of an increased IL-12 response that in turn led to the induction of higher numbers of IFN-gamma producing CD4(+)T cells, the principal orchestrators of SK. Our results indicate that the severity of HSV induced immunopathological lesions may be mainly the consequence of IL-12 driven Th1 T cell reactions rather than the action of IL-17 producing cells controlled by IL-23.

Application of FGF-2 to modulate herpetic stromal keratitis.

PURPOSE: Herpetic stromal keratitis (SK) is a tissue destructive eye lesion caused by infection of herpes simplex virus-1 (HSV-1). One step by which HSV-1 enters the cell is through binding to surface heparan sulfate proteoglycans (HSPG), a process that can be inhibited by fibroblast growth factor 2 (FGF-2). The current study examined the effect of FGF-2 application on the outcome of ocular HSV infection. METHODS: Vero cells were infected with HSV-1 after preincubation with FGF-2 protein, and viral infectivity was determined by plaque reduction assay. In an in vivo study, mice were ocularly treated with FGF-2 before (plasmid DNA) or after (recombinant protein) HSV-1 infection, and SK lesion severity was observed. RESULTS: Whereas FGF-2 had excellent antiviral effects in vitro, it was without significant inhibitory effects when given as plasmid DNA encoding FGF-2 (100 microg/application) onto the cornea of the susceptible mouse (BALB/c) before virus infection. Only minor antiviral effects of FGF-2 in vivo were initially observed. Interestingly, topical treatment of recombinant FGF-2 protein (50 ng, two times daily until day 10 postinfection) into HSV-1-infected corneas significantly reduced SK lesion severity and incidence, presumably by promoting epithelial ulcer healing. CONCLUSIONS: These results suggest that treatment of FGF-2 has therapeutic effects on herpetic SK progression via its role in wound healing.

Viruses and autoimmunity.

Viruses have been suspected as causes and contributors of human autoimmune diseases (AID), although direct evidence for the association is lacking. However, several animal models provide strong evidence that viruses can induce AIDs as well as act to accelerate and exacerbate lesions in situations where self-tolerance is broken. Many models support the hypothesis by acting as molecular mimics that stimulate self-reactive lymphocytes. Mimicry alone is usually inadequate and with human AID, no compelling evidence supports a role for viruses that are acting as molecular mimics. Alternative mechanisms by which viruses participate in autoimmunity are non-specific, involving a mechanistically poorly understood process termed bystander activation or perhaps viral interference with regulatory cell control systems. This review briefly discusses examples where viruses are involved, taking the view point that molecular mimicry is over emphasized as a critical mechanism during AID pathogenesis.

A tale of 2 alpha-herpesviruses: lessons for vaccinologists.

Of the 8 known herpesviruses that affect human beings, we only have successful vaccines against varicella zoster virus. This brief review compares the pathogenesis of varicella zoster virus with that of the closely related alpha-herpesviruses herpes simplex virus 1 and 2, for which we have no satisfactory vaccines. The main objective of this review is to learn lessons from the success of varicella zoster virus vaccine that could be exploited for the development of successful vaccines against herpes simplex virus and perhaps against other herpes viruses.