This study will enable the development of methodologies to effectively control the spread of such strains and to treat infections caused by them
Indian Institute of Technology Jodhpur research team led by Dr Shankar Manoharan, Assistant Professor, Department of Bioscience & Bioengineering, are studying the mechanisms behind the virulence (the ability to cause disease) and antibiotic resistance (ability to resist killing by antibiotics) of a dangerous bacteria called Klebsiella pneumoniae.
The studies, performed in collaboration with scientists from the All India Institute of Medical Sciences, AIIMS Jodhpur and Vellore Institute of Technology, VIT Vellore, use genomics and molecular biology approaches to identify new genes responsible for the bacteria’s potency. Klebsiella pneumoniae is one of the pathogens on the World Health Organisation’s priority list and is a significant cause of hospital-acquired diseases such as pneumonia, bloodstream infections, and infections among ICU patients and newborns. Because of its high virulence and antibiotic resistance, the management and treatment of Klebsiella pneumoniae have challenged the medical and scientific community worldwide.
The findings of this research have been published recently in the journal, Microbiology Spectrum. The paper has been co-authored by Dr Shankar Manoharan along with his PhD scholars-Aastha Kapoor, Tamal Dey, and Ardhendu Chakrabortty, along with Prof. Vijayalakshmi Nag of AIIMS Jodhpur, and Dr Karthikeyan Sivashanmugam of VIT, Vellore.
Explaining the basis of the virulence of the bacteria, Dr Manoharan said, “One of the ways in which Klebsiella pneumoniae escapes the body’s immune system, and antibiotics is by producing an extremely sticky and viscous protective covering (hypermucoviscosity) around itself.”
Hypermucoviscosity can be identified by the string test, in which a bacterial colony growing in laboratory media is touched using an applicator, which is then slowly lifted off the colony. If a sticky string of 5 mm or more excellent extends from the colony to the applicator, the bacteria is hypermucoviscous and highly virulent. The researchers studied a strain of the bacteria called P34, isolated from the cystic lesion of a patient at a tertiary care hospital in Jodhpur and found that it produced a string of 65 mm long.
It has been known that the capsule and mucous-like protections in Klebsiella pneumoniae are driven by the rmpA, rmpA2, rmpC, and rmpD genes. However, phenotyping and genomic analysis of P34 by the IIT Jodhpur team showed that this strain does not have any of these genes. This means that there are genes other than the rmp family of genes that are responsible for the hypermucoviscosity and virulence of the bacterium.
Knowing that other genes and mechanisms could play a part in the virulence of Klebsiella pneumoniae, the researchers continue to study variations (mutants) of the P34 strain of the bacteria to understand the correlation between the mucous formation and the genes present or absent. The team have also identified mutants that have lost this unusual stickiness due to mutations in specific genes.
Highlighting the future trajectory of their work, Dr Manoharan said, “We are currently studying these mutants and disrupted genes to explain the potentially new mechanisms behind this unusual sticky and viscous covering of Klebsiella pneumoniae P34.” Such understanding will enable the development of methodologies to effectively control the spread of such strains and treat infections caused by them.
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