Revealed: Dual Functional Characteristics Of Escherichia Coli Outer Membrane Protein Wzi And Its Implications In The Design Of Novel Antibiotics
Project Description :

The emergence of multidrug resistance in bacteria is a major cause of infection and mortality worldwide. in gram-negative bacteria, capsules are one of the major virulent determinants that are involved in the evasion of host immune response. surface-association of cps offers impermeability to antibiotics, thus, eases the bacteria to establish infection in the host. however, the underlying mechanism behind how cps aids the bacteria to evade host immune response is poorly understood. inhibiting the cps biogenesis or surface exportation or its attachment to the bacterial surface may be an attractive strategy to generate avirulent gram-negative bacterial strains. here, we focus on multidrug resistant gram-negative escherichia coli (e. coli), which is a common cause for urinary tract infections (including infections in the kidney), bloodstream infection, intra-abdominal infections such as peritonitis, skin and soft tissue infections, neonatal meningitis, diarrhea and food borne infections. recent survey among 194 who member states in 2014 clearly indicates that e. coli has evolved resistance against third-generation cephalosporins and fluoroquinolones, the two major antibacterial drugs that are currently used to treat e. coli infections (who 2014). reports on 'emergence of carbapenem resistance' in e. coli are quite alarming, as it is the antibiotic of 'last resort'. we have recently identified that an e. coli outer membrane protein wzi that acts as an anchor for cps onto the bacterial surface (viz., a lectin) also exhibits a bidirectional passive water conduction property (viz., a porin). such a dual functional role of wzi was not realized earlier due to the occluded pore, a property that can be used to treat e. coli infections. we have observed that while five water specific entry points distributed across extracellular (three) & periplasmic (two) faces regulate the water diffusion involving different mechanisms, a luminal hydrophobic plug governs water permeation across the channel. water conduction characteristics of wzi also explain the prerequisite for the protein to exhibit such a dual role. when the osmotic pressure becomes high due to the surface accumulation of cps, water is transported from inside the bacteria to outside to dilute and spread the concentration of cps and avoid the rupturing of the cell. this keeps the cps in a hydrated condition and prevents further accumulation of cps on the bacterial surface. however, when the concentration of cps is less on the surface, water is transported from outside to inside of the bacteria to normalize the pressure. thus, optimal concentration of cps can be maintained through osmo regulation character of wzi. further, we are able to pinpoint that an “yqf” triad that is located on the bacterial surface can be the point of cps surface anchorage. thus, a drug molecule that can either interfere with the water conduction by wzi or the attachment of cps to ‘yqf’ may aid in reducing the bacterial virulence and make them susceptible to antibiotics or host immune response.

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Project Details :
  • Date : Oct 18,2016
  • Innovator : Shivangi Sachdeva
  • Team Members : Narendar Kolimi
  • Guide Name : Dr. Thenmalarchelvi Rathinavelan
  • College : Indian Institutes of Technology, Hyderabad
  • University : Indian Institutes of Technology, Hyderabad
  • Submission Year : 2017
  • Category : Bioengineering / Biotech
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