Author: Nitin Bayal
National Centre for Cell Science, Pune
My presumptions about leprosy were incorrect! Books and documentaries have spoken plenty in silence but still incomplete.
In the middle ages, it was one of the most feared diseases and was once considered as “Living Death”. There was a time when prevailing religious concepts kept our attention away from finding the root cause of leprosy transmission and religious institutions influenced the health and disease affairs. Illness due to leprosy was accepted as a curse from God or bad luck, just as many different phenomena that were not linked to cause-and-effect theory credited to the act of god, forcing people to plead and compensate for this unexplained experience.
Although after new advances in science and technology came into existence, it became difficult to arguably justify scientific reasoning with superstitions. The dreadful infections in leprosy have much more to say than eradication objectives. Prior to perusing a Ph.D. at National Centre for Cell Science, Pune; I knew very little about leprosy and Mycobacterium leprae, the causative organism of leprosy. Leprosy which causes poor wound healing, nerve damage and if left untreated it results in permanent disfigurement or loss of body parts, has for long been associated with a social stigma.
In India, for ages, ayurvedic preparations known as chaulmoogra oil was used to treat leprosy, and with the introduction of western medicine prescription drugs like Dapsone and Rifampicin, the catalog of every possible physical and chemical agent to indiscriminately kill the bad microbes is ever-expanding.
It is known to us that a leprosy patient loses the ability to feel the temperature change and pain in the affected area on their body; with the current understanding on the subject, we discovered some mysterious insights on leprosy research that encouraged skin microbiome research in leprosy. We added a brief note on each idea discussed in our research group. I tried to understand the diseased states, current therapeutics, and the problems that challenge scientists in this field.
M. leprae slowly gets resistant to new drugs and hence, raises concerns for a more severe form of the disease. In 1982, World Health Organization (WHO) released Multi-Drug Therapy (MDT) guidelines that dictate the planning and execution to eradicate leprosy. There is also the addition of newer drugs into the arsenal along with MDT treatment. Recently, scientists and clinicians speculated India accounts for 66% of leprosy patients worldwide. To challenge leprosy, WHO accelerated a global leprosy strategy for 2016-2020. A team of scientists led by Dr. GP. Talwar at All India Institute of Medical Science (AIIMS); New Delhi developed a vaccine in the 1970s that is finally recommended to launch on 2nd October 2019 after 36 years of testing in the clinical trials. As of now, it is well recognized that leprosy elimination has never been achieved actually in India.
Moreover, the frequency of resistant mutants also varies to different drugs, MDT treatment also kills the bacteria that are naturally resistant to drugs on the affected sites. It also affects the normal skin bacterial community.
Skin is the primarily affected organ in leprosy. This is where the skin microbiome plays its role to support normal homeostasis. The microbiome consists of an ecosystem of billions or trillions of microorganisms living in and on our bodies including skin. There is growing evidence that skin infections and drug abuse change or disturbs the skin microbiota in various types of skin pathological conditions like acne, eczema, psoriasis, skin allergies, and wounds.
We knew that both research scientists and clinicians play a critical role in the successful completion of studies on human subjects through mutual collaborations. While communicating with scientists, dermatologists, and workers of all levels at different NGOs, we finally found our collaborations in 2015 with leprosy clinics at LEPRA and TLM organizations for clinical samples. Then it was followed by regular meetings with patients and leprologists at leprosarium, where patients are kept for their treatment. The situation of patients was horrible because of their constant suffering, thus to understand the relationship between the skin microbiome and M leprae infection, researchers at DBT-National Centre for Cell Science and Bio-Sciences R&D, TCS Innovation Labs, Pune also collaborated to conduct a new study on the skin microbial communities from lesional and non-lesional skin of Indian leprosy patients undergoing multi-drug regimen treatment and healthy individuals covering two different geographical locations viz. Hyderabad and Miraj in India.
We obtained ethical and biosafety clearances and collaborated with Dr. Vijayalakshmi Valluri at LEPRA, Hyderabad and, Dr. Rohini Suryavanshi at TLM, Miraj, Maharashtra for clinical samples. We collected skin samples and extracted microbial DNA. We have used DNA sequencing methodologies and analysis tools to define the cutaneous microbiota. Our study has shown that the skin microbiota of healthy persons and leprosy patients have significant differences in its variety and abundance. The reasons also include the role of various external and internal factors comprising skin pH, skin thickness, skin moisture, hygiene, climate, etc. The photograph shown above was taken with consent at Richardson leprosy hospital, Miraj, Maharashtra, and pixelated to maintain the confidentiality of the leprosy patient.
Together with Dr. Milind S. Patole as doctoral co-supervisor, Dr. Dhiraj Paul, and Mr. Sunil Nagpal, one of my colleagues at TCS Innovation Labs, we have completed computational analysis on high-throughput sequencing data. We have published the first report on the structure of skin microbiota from India in Springer Nature journals i.e., Nature Scientific Data and Nature Scientific Reports journals. The corresponding authors, Dr. Shekhar C. Mande is Secretary DSIR and Director General, CSIR, New Delhi and Dr. Sharmila S. Mande is Chief Scientist and Head of Bio-Sciences R&D, TCS Research, Pune. They are leading scientists and specialized in Structural Biology and Microbiome research respectively.
Our analysis shows differences in the microbiota of affected and unaffected sites on the skin of leprosy patients and similarities among healthy persons irrespective of our sampling sites in India. Microbial diversity probes a distinct depletion of Staphylococcus genera in samples from affected sites of leprosy patients. Major abundant bacteria observed were Pseudomonas, Staphylococcus, Paracoccus, Brevundimonas, Limnobacter, Methylobacterium, Propionibacterium, Corynebacterium, Kocuria, and Streptococcus on the leprosy patient’s skin. It also shows a significant decline in firmicutes-related bacteria in leprosy patients in comparison to healthy individuals. It was a strange coincidence when M leprae attacks and occupy spaces in human bodies by either high exposure to infections or low immunity or both situations. M leprae is very intelligent, being a metabolically challenged bacterium it has managed to survive harsh conditions and still a mystery for the researchers for its cultivation in laboratory conditions. We are also afraid of liberal use of antibiotics and antiseptics that not only results in the extinction of some good bacteria but also kept the fortunate ones under constant threat.
The aspect of working with microbiome research can help skin microbiome transplantation science that corresponds to better disease management and diagnosis. A healthy microbiome protects humans from harmful settlers and infections by pathogens or opportunistic microorganisms.
Nowadays, many ventures are introducing probiotic products in the skin healthcare system and focusing on implications of skin’s health and appearance. The future of treating skin diseases is hopeful from microbiome research. However, despite these positive developments, measures to improve the healthcare system are also required. Humans often err in their haste. After all the great riches of leprosy are its paradoxes. If we are losing this time that will be another paradox, our luck may also prove contrary.
Author Bio: Nitin is a microbiome researcher at DBT-National Institute of Immunology, New Delhi. His interest mainly focus on data analytics in healthcare sector. He is an acclaimed scientific illustrator with a well disposed eye for art in daily lives. Nitin holds a degree of Master of Science in Molecular and Human Genetics and published his Ph.D work on leprosy research. His work is guided by a need to rationalize, make things beautiful, combine science with art and connect ideas.
Area of research: Skin biology, microbiome, sequencing technologies
Google Scholar link: https://scholar.google.com/citations?user=79o59fkAAAAJ&hl=en
Twitter handle: @BayalNitin
A synthetic peptide (bioconjugate) substrate for cell surface enzyme Sortase A exhibits significant anti-biofilm activity, which can be utilized to make anti-biofilm surfaces for clinical applications and indwelling medical devices.
The study conducted by a group of researchers from NIPER Guwahati(National Institute of Pharmaceutical Education and Research, Guwahati), demonstrated that a Sortase-A mediated bioconjugate can inhibit biofilm formation and combat hospital acquired infections, the findings of the study was published in the journal Frontiers in Microbiology.
Staphylococcus aureus one of the most notorious pathogens which is frequently associated with nosocomial infections imposing serious risk to immune-compromised patients, because of its ability to colonize at the surface of indwelling medical devices such as catheters, pacemakers, contact lenses, and dentures by biofilm formation. Staphylococcus aureus is known to form multilayered adherent biofilm to the surface of indwelling medical devices including catheters and medical implants, expressing series of toxins which makes them tolerant toward host defense mechanisms and common antibiotics and Biofilm formation on both natural and artificial surfaces is one of the most important virulence mechanisms of many bacterial pathogens, as it guards the bacteria against antibiotic therapy, and thus considered to be the major cause of nosocomial infections especially in post-surgical and immune-compromised patients and is associated with significant mortality in hospitalized patients.
Sortase A is one of the most important enzymes present on the cell surface of Gram positive bacteria including S. aureus. Sortase A recognizes the LPXTG motif present at the C-terminus of cell surface proteins and recruits them to the peptidoglycan cell wall
building block, lipid II, thus search for molecules that can inhibit Sortase A is one of the promising approaches for the development of innovative strategies to impair bacterial virulence and biofilm formation
In the present study, the study group synthesized a novel 6His-LPETG peptide and incorporated it on the cell wall of S. aureus and evaluated the ability of this peptide to inhibit biofilm formation by Gram positive bacteria. Their study exhibits significant anti-biofilm activity of this peptide having an LPETG motif, and it shows that the present mechanism could further be tested against other Gram positive bacteria having Sortase A enzyme.
The research team further envisioned that the 6-His epitope along with LPETG motif will allow grafting the surface of the bacteria with epitopes which can be utilized to target the bacteria using 6-His antibodies. In their communication the researchers explained that, "the advantage of our strategy is that it is neither altering any biological process within the bacteria nor inhibiting it. Thus, it is not putting any selective pressure on bacterial population which is one of the major concerns of antibiotic therapy. Our peptide is using bacterial machinery to recruit itself on the cell surface and then hinder the process of biofilm formation". Thus, the strategy can potentially be developed and utilized to make anti-biofilm surfaces for clinical applications.
*The study was funded by NIPER seed fund, Government of India*
Poonam Kumari, Yutika Nath, Upadhyayula Surayanarayana Murty, Velayutham Ravichandiran and Utpal Mohan. Sortase A Mediated Bioconjugation of Common Epitopes Decreases Biofilm Formation in Staphylococcus aureus. Frontiers in Microbiology. 30 July 2020 | https://doi.org/10.3389/fmicb.2020.01702
P.S. Content edited for style and length
Hello! My name is Arunabha Banerjee, and I am the mind behind Biologiks. Leaning new things and teaching biology are my hobbies and passion, it is a continuous journey, and I welcome you all to join with me