IMPACT OF OUR WORK
Research group publications (June 2018 - august 2021)
New work and repository alert!
Mhade S, Panse S, Tendulkar G, Awate R, Kadam S, Kaushik KS. Biorxiv (2021).
AMPing up the game: An in silico approach to identifying AMPs with potential anti-biofilm activity.
We present an in silico approach, based on open-source tools, to identify AMPs with potential anti-biofilm activity. This approach is developed using the sortase-pilin machinery, important for adhesion and biofilm formation, of the multidrug-resistant, biofilm-forming pathogen C. striatum as the target. Using homology modeling, we modeled the structure of the C. striatum sortase C protein, resembling the semi-open lid conformation adopted during pilus biogenesis. Next, we developed a structural library of 5544 natural and synthetic AMPs from sequences in the DRAMP database. From this library, AMPs with known anti-Gram positive activity were filtered, and 100 select AMPs were evaluated for their ability to interact with the sortase C protein using in-silico molecular docking. Based on interacting residues and docking scores, we built a preference scale to categorize candidate AMPs in order of priority for future in vitro and in vivo biofilm studies.
Biofilm-AMP (A structural repository of AMP models and protein-peptide interactions relevant for biofilm studies
Mhade S, Panse S, Tendulkar G, Awate R, Kaushik KS (2021).
The resources and data generated in this approach are freely available in Biofilm-AMP (B-AMP), a user-friendly, search-enabled repository of AMP structures and AMP interactions with biofilm targets. The repository includes predicted structures for 5544 AMPs, searchable by their Pep ID, DRAMP ID, name and source, and a separate subset of 2534 AMPs filtered by known anti-Gram positive activity. For each peptide, the repository includes FASTA files, PDB files, and predicted and chosen 3D models. For the 100 AMPs selected for in silico molecular docking, the repository hosts input & output PDBQT files, images, and a text file detailing hydrogen interactions.
Radhika and Nizam presented their recent work on in vitro systems to study biofilms at the EMBL Microbiology Conference (virtual)
Get in touch with us for any Qs!
Kadam S, Madhusoodhanan V, Dhekane R, Bhide D, Ugale R, Tikhole U, Kaushik K. Biofilm (2021).
Milieu Matters: An in vitro wound milieu to recapitulate key features of, and probe new insights into, mixed-species bacterial biofilms.
Based on previous reports of clinical wound fluid composition, we have developed an in vitro wound milieu (IVWM) that includes, in addition to serum (to recapitulate wound fluid), matrix elements and biochemical factors. We demonstrate that the IVWM recapitulates widely reported in vivo biofilm features such as metabolic activity, increased antibiotic tolerance, 3D structure, and interspecies interactions for single- and co-species biofilms. Further, the IVWM is simple to formulate, uses laboratory-grade components, and is compatible with standard biofilm assays. Given this, it holds potential as a tractable approach to study wound biofilms under host-relevant conditions.
Karishma worked with Dr. Celia Fortunae Rodrigues (University of Porto, Portugal) and Dr. Caitlin Light (Binghamton University, USA) to put together a Special Issue on Biofilms in Wounds: New Advances in Therapy and in Healing Management for Biomedicines (2021).
Looking beyond the smokescreen: Can the oral microbiome be a tool or target in the management of tobacco-associated oral cancer?
Kadam S, Madhusoodhanan V, Patwardhan S, Kaushik KS. eCancer (2021).
This is a new focus area of our group!
Kadam S, Madhusoodhanan V, Bandgar A, Kaushik K. Front Pharmacol (2020).
From Treatise to Test: Evaluating Traditional Remedies for Anti-Biofilm Potential
We identified and reconstituted plant-based medicinal formulations from historical treatises of Indian traditional medicine, and analyzed their efficacy using microtiter based assays, that constitute the cornerstone of biofilm studies. Through this study, we provide insights into considerations and challenges relevant to the "treatise to test" phase of the "ancientbiotics" pipeline.
A more human-relevant approach that reduces the use of animal products in research.
Kadam S, Madhusoodhanan V, Kaushik K. Biotechniques (2020).
Reduced-serum based approaches for contact-based co-culture of human dermal fibroblasts and epidermal keratinocytes.
In this methods paper, we have developed two reduced-serum based approaches (1-2% serum), using commonly-available media components, to support the contact-based co-culture of HDFa and HaCaT cells. Taken together, these formulations result in effective concentrations of 1-2% FBS, representing a 5–10 fold reduction in serum concentration as compared with previous studies (using up to 10% serum).
Kadam S, Nadkarni S, Lele J, Sakhalkar S, Mokashi P, Kaushik K (2020).
Bioengineered platforms for Chronic Wound Infection Studies: How can we make them more Human-Relevant? Front Bioeng Biotechnol.
Using chronic wounds as an example, we discuss that infection microenvironments can be bioengineered using a two-compartment approach, with the upper compartment the ‘infected wound bed’ and the lower compartment the capillary immune interface.
Franco-Duarte R, Černáková L, Kadam S, Kaushik K, et al (2019). Advances in chemical and biological methods to identify microorganisms – from past to present. Microorganisms.
This invited review discusses methods of detection and identification of microorganisms, from past methods based on microbial isolation to current approaches employing molecular techniques. An international collaboration with Portugal, Iran, Italy, Poland and Brazil; we contributed to the section on molecular diagnostic tools.
Kadam S, Shai S, Shahane A, Kaushik K (2019). Recent advances in non-conventional antimicrobial approaches for chronic wound biofilms: Have we found the ‘chink in the armor’? Biomedicines.
We discuss recent therapeutic approaches for chronic wound biofilms that go beyond antibiotics, focusing on non-conventional strategies that directly kill or inhibit microbes or modify infection microenvironmental factors. We propose that most approaches will serve as adjunct therapies with antibiotics, while nanoantimicrobials can offer a new treatment paradigm.
Kaushik K, Kadam S (2019). Abandon or Administer? Moving Beyond Oversimplified Approaches and Developing Strategies that Target the Composite Infected Wound Microecosystem. Letter to the Editor. Wounds.
In this Letter to Editor, we argue that an all-or-none approach to the use of antibiotics is reductionist, and therapeutics need to account for and target the complexity of the infection state.
Kaushik K (2019). Defining the path of physician-scientist. Nature Medicine.
Featured as part of Nature Medicine's 25th year anniversary series to highlight 25 physician-scientists' the world over.
Our previous publications (prior to 2018)
Hutchison J, Kaushik K, Lilleholm T, Bakhtiari L, Gordon VD (2018). Increased production of the extracellular polysaccharide Psl can give a growth advantage to Pseudomonas areruginosa under low iron conditions. bioRxiv. https://www.biorxiv.org/content/10.1101/355339v1.
Using quantitative time-lapse confocal microscopy and image analysis of biofilm growth, my work discovered that aggregates of P. aeruginosa (red) have a growth advantage over single cells in the presence of S. aureus (yellow), under low-iron conditions. Our results suggested that this effect was linked to the high EPS content of aggregates, and its ability to posit iron acquisition, likely from S. aureus.
Kaushik K, Stolhandske J, Shindell O, Smyth H, Gordon VD (2016). Tobramycin and Bicarbonate synergize to kill planktonic Pseudomonas aeruginosa, but antagonize to promote biofilm survival. npj Biofilms and Microbiomes.
Using checkerboard assays and an interpolated surface methodology, I determined that bicarbonate synergizes with tobramycin to enhance killing of planktonic bacteria, but antagonizes to promote biofilm survival. This has clinical implications since bicarbonate is being evaluated as a replacement therapy for Cystic Fibrosis
Kaushik K, Ratnayeke N, Katira P, Gordon VD (2015). The spatial profiles and metabolic capabilities of microbial populations impact the growth of antibiotic-resistant mutants. J R Soc Interface.
I discovered that microbial population structure, via density and spatial organization, impacts the survival of antibiotic-resistant mutants, in the presence of antibiotic. This effect is mediated by alkaline metabolic by-products of bacterial growth, likely ammonia or amines, that enhance the efficacy of aminoglycosides against antibiotic-resistant mutants. This opens the possibility that microbial population structure and nutrient environments could enhance antibiotic efficacy
Kaushik K, Kessel A, Ratnayeke N, Gordon VD (2015). A low-cost, hands-on module to characterize antimicrobial compounds using an interdisciplinary, biophysical approach. PLoS Biology.
As part of a hands-on school held at the International center for Theoretical Physics, Trieste, Italy, I developed an ultra-low cost, hands-on experimental module that combines biology experiments with a physics-based analytical model to test antimicrobial compound and characterize the active ingredient. In doing so, this module addresses the paucity of structured training programs that integrate diverse fields, and is suitable for implementation in resource-limited settings
Hutchison J, Rodesney C, Kaushik K, Le H, Hurwitz D, Irie Y, Gordon VD (2014). Single cell control of initial spatial structure in biofilm development using laser trapping. Langmuir.
Using laser-trapping, we present a method for growing biofilms from initiating cells controlled with single-cell precision. For co-pathogens, P. aeruginosa and S. aureus native growth, motility and surface adhesion of positioned microbes is preserved, and trapping and placing bacteria on surfaces reveals the effects of spatial structure on bacterial growth
First Large-Scale Characterization of Clinical Varicella Zoster (Chicken Pox) strains in India
Kaushik K, Lahiri KK, Chumber SK, et al (2008). Molecular characterization of clinical varicella-zoster strains from India and differentiation from the Oka vaccine strain. Jpn J Infect Dis.
This study was the first large-scale characterization of clinical VZV strains in India. Using PCR-RFLP and Gene Sequencing targeting two ORFs, I determined that circulating Indian VZV strains were genotypically distinct from the vaccine Oka strain licensed for use. This work opened the possibility of developing strain-specific VZV vaccines for India.
Kaushik K, Lahiri KK, Kumar S, et al (2008). Differentiation of wild-type varicella- zoster strains from India and the Oka vaccine strain using a VZV ORF-62 based PCR-RFLP Technique. Braz J Infect Dis.
I developed a PCR-RFLP approach to distinguish Indian VZV strains from the vaccine Oka strain using a single ORF based analysis, which reduces time-cost-resources compared to the two ORF approach.
Dr. Karishma was awarded the Ranbaxy Young Science Scholar award (2008) from Nobel Laureate Prof. David Baltimore for this work.
Clinical Publications and Case Reports
Kaushik K, Kapila K, Chumber SK (2013). Photo Quiz: Lady in Red. J Clin Microbiol 51: 3915.
Kaushik K, Kapila K, Praharaj AK (2011). Shooting Up: The interface of microbial infections and drug abuse. J Med Microbiol 60: 408-422.
Kaushik K, Kapila K (2009). Women in Medical Microbiology: Reflections on contributions. Indian J Med Microbiol 27: 285-288.
Kaushik K, Kapila K (2009). Laboratory microbiology to clinical microbiology: Are we ready for the transition? Indian J Med Microbiol 27: 378-379.
Kaushik K, Kumar S, Kapila K, et al (2007). Tuberculous brain abscess in a patient with HIV infection. Indian J Tuberc 54: 196-198.
Chumber SK, Kaushik K, Savy S (2007). Bacteriological profile of street foods in Pune. Indian J Pub Health 51.