Novel Drugs Against Infectious Bacterial Biofilms
Authors: Vipin Chandra Kaliaa,b* , Shikha Koula,b
aMicrobial Biotechnology and Genomics, CSIR - Institute of Genomics and Integrative Biology (IGIB), Delhi University Campus, Mall Road, Delhi-110007.
bAcademy of Scientific & Innovative Research (AcSIR), 2, Rafi Marg, Anusandhan Bhawan, New Delhi- 110001.

Bacteria causing infectious diseases in human beings are a major cause of worry among Health Departments. These pathogens form biofilms through quorum sensing. Biofilm protects bacterial pathogen against antibiotics. They become 'resistant' to even very high doses of antibiotics. However, once exposed by disrupting the biofilm, they become susceptible to very low doses of antibacterial. Biofilms are made up of exopolysaccharides, proteins and lipids. Enzymes which can degrade these biofilms can be exploited as drugs against infectious disease causing pathogens.


Many bacterial surface proteins responsible for biofilm formation highlighted the potential of proteases as important in inhibiting this process. Secretary proteases such as serine protease, staphopain and auroelysin can disrupt Staphylococcal biofilms. Esp protease is effective against human receptor proteins like vitronectin, fibrinogen and fibronectin, which play a significant role in infection and colonization. Cysteine proteinase can degrade many substrates, which include: extracellular matrix, chemokines cytokines, and immunoglobulins. Lysostaphin, an endo-peptidase acts on bacterial peptidoglycan and kill them within the biofilm. Lysostaphin in combination with antibiotics such as oxacillin have synergistic effect against methicillin resistant bacteria. Commercially produced serine proteases like Trypsin and Proteinase K disassemble bacterial biofilms formed byMicrobacterium, Acinetobacter, Dokdonia and Shewanella. Biofilms formed by Gram-positive bacteria were attacked by commercial proteases - Neutrase, Alcalase, and Flavourzyme obtained from Aspergillus and Bacillus species. Other proteases of interest are metallo-proteases - serratiopeptidase and carboxypeptidase A.

Bacteria as inhibitors

Bdellovibrio bacteriovorus has the unique characteristic to act as anti-pathogenic agent. Extracellularly produced protease could degrade and inhibit biofilms. Serine proteases and DNAse produced by B. bacteriovorus prevent bacterial infections caused by Staphylococcus, Pseudomonas, Aggregatibacter and Fusobacterium.

Bacteriophages as proteolyic agents

Bacteriophages produce lytic enzyme (lysine) to control antibiotic resistant bacteria especially those which harbour catheters, animal tissue and mucosal surfaces. Single-domain lysin - CHAPK and multi-domain lysins such as SAL-2 and φ11 lysin control bacterial biofilms. The endopeptidase cleaves cell wall peptidoglycan and control infection.


There are many other ways also to inhibit bioflilm formation and dispersal of those already formed: DNases, hydrolases, peptides, etc.


  1. Ahiwale SS, Bankar AV, Tagunde S, Kapadnis BP (2017) A bacteriophage mediated gold nanoparticle synthesis and their anti-biofilm activity. Indian J Microbiol 57:188-194. doi: 10.1007/s12088-017-0640-x
  2. Azman CA-S, Othman I, Fang C-M, Chan K-G, Goh B-H, Lee L-H ( 2017) Antibacterial, anticancer and neuroprotective activities of rare actinobacteria from mangrove forest soils. Indian J Microbiol 57:177-187. doi: 10.1007/s12088-016-0627-z
  3. Begum IF, Mohankumar R, Jeevan M, Ramani K (2016) GC-MS analysis of bioactive molecules derived from Paracoccus pantotrophus FMR19 and the antimicrobial activity against bacterial pathogens and MDROs. Indian J Microbiol 56:426-432. doi: 10.1007/s12088-016-0609-1
  4. Boles BR, Horswill AR (2011) Staphylococcal biofilm disassembly. Trends Microbiol 19:449-445 doi: 10.1016/j.tim.2011.06.004
  5. Chagnot C, Zorgani MA, Astruc T, Desvaux M (2013) Proteinaceous determinants of surface colonization in bacteria: bacterial adhesion and biofilm formation from a protein secretion perspective. Front Microbiol 4:303. doi: 10.3389/fmicb.2013.00303
  6. Elchinger PH, Delattre C, Faure S, Roy O, Badel S, Bernardi T, Taillefumier C, Michaud P. (2014) Effect of proteases against biofilms of Staphylococcus aureus and Staphylococcus epidermidis. Lett Appl Microbiol 59:507-513. doi: 10.1111/lam.12305
  7. Fenton M, Keary R, McAuliffe O, Ross RP, O'Mahony J, Coffey A ( 2013) Bacteriophage-Derived peptidase eliminates and prevents Staphylococcal biofilms. Int J Microbiol 2013:625341. doi:10.1155/2013/625341
  8. Gui Z, Wang H, Ding T, Zhu W, Zhuang X, Chu W (2014) Azithromycin reduces the production of α-hemolysin and biofilm formation in Staphylococcus aureus. Indian J Microbiol 54:114-117. doi: 10.1007/s12088-013-0438-4
  9. Hernández-SaldanÌ'a OF, Valencia-Posadas M, de la Fuente-Salcido NM, Bideshi DK, Barboza-Corona JE (2016) Bacteriocinogenic bacteria isolated from raw goat milk and goat cheese produced in the Center of México. Indian J Microbiol 56:301-308. doi: 10.1007/s12088-016-0587-3
  10. Iwase T, Uehara Y, Shinji H, Tajima A, Seo H, Takada K, Agata T, Mizunoe Y (2010) Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature 465:346-349. doi: 10.1038/nature09074
  11. Jeyanthi V, Velusamy P (2016) Anti-methicillin resistantStaphylococcus aureus compound isolation from halophilic Bacillus amyloliquefaciens MHB1 and determination of its mode of action using electron microscope and flow cytometry analysis. Indian J Microbiol 56:148-157. doi: 10.1007/s12088-016-0566-8
  12. Kalia VC (2013) Quorum sensing inhibitors: an overview. Biotechnol Adv 31:224-245. doi: 10.1016/j.biotechadv.2012.10.004
  13. Kalia VC (2014) Microbes, antimicrobials and resistance: The battle goes on. Indian J Microbiol 54:1-2. doi: 10.1007/s12088-013-0443-7
  14. Kalia VC, Prakash J, Koul S, Ray S (2017) Simple and rapid method for detecting biofilm forming bacteria. Indian J Microbiol 57:109-111. doi: 10.1007/s12088-016-0616-2
  15. Kalia VC, Purohit HJ (2011) Quenching the quorum sensing system: potential antibacterial drug targets. Critical Rev Microbiol 37:121-140. doi: 10.3109/1040841X.2010.532479
  16. Koul S, Kalia VC (2017) Multiplicity of quorum quenching enzymes: A potential mechanism to limit quorum sensing bacterial population. Indian J Microbiol 57:100-108. doi: 10.1007/s12088-016-0633-1
  17. Koul S, Prakash J, Mishra A, Kalia VC (2016) Potential emergence of multi-quorum sensing inhibitor resistant (MQSIR) bacteria. Indian J Microbiol 56:1-18. doi: 10.1007/s12088-015-0558-0
  18. Kumar P, Patel SKS, Lee JK, Kalia VC (2013) Extending the limits of Bacillus for novel biotechnological applications. Biotechnol Adv 31:1543-1561. doi: 10.1016/j.biotechadv.2013.08.007
  19. Kumar R, Koul S, Kumar P, Kalia VC (2016) Searching biomarkers in the sequenced genomes of Staphylococcus for their rapid identification. Indian J Microbiol 56:64-71.doi:10.1007/s12088-016-0565-9
  20. Monnappa AK, Dwidar M, Seo JK, Hur JH, Mitchell RJ (2014)Bdellovibrio bacteriovorus inhibits Staphylococcus aureus biofilm formation and invasion into human epithelial cells. Sci Rep 4: 3811. doi: 10.1038/srep03811
  21. Mootz JM, Malone CL, Shaw LN, Horswill AR (2013) Staphopains modulate Staphylococcus aureus biofilm integrity. Infect Immun 81:3227-3238. doi: 10.1128/IAI.00377-13
  22. Sharma A, Lal R (2017) Survey of (Meta)genomic approaches for understanding microbial community dynamics. Indian J Microbiol 57:23-38. doi:10.1007/s12088-016-0629-x
  23. Sugimoto S, Iwase T, Sato F, Tajima A, Shinji H, Mizunoe Y ( 2011) Cloning, expression and purification of extracellular serine protease Esp, a biofilm-degrading enzyme, from Staphylococcus epidermidis. J Appl Microbiol 111:1406-1415. doi: 10.1111/j.1365-2672.2011.05167.x
  24. Varsha KK, Nishant G, Sneha SM, Shilpa G, Devendra L, Priya S, Nampoothiri KM (2016) Antifungal, anticancer and aminopeptidase inhibitory potential of a phenazine compound produced by Lactococcus BSN307. Indian J Microbiol 56:411-416. doi: 10.1007/s12088-016-097-1
  25. Wadhwani SA, Shedbalkar UU, Singh R, Vashisth P, Pruthi V, Chopade BA ( 2016) Kinetics of synthesis of gold nanoparticles by Acinetobacter sp. SW30 isolated from environment. Indian J Microbiol 56:439-444. doi: 10.1007/s12088-016-0598-0

About Author / Additional Info:
Researchers in Microbial Biotechnology and Genomics at CSIR-IGIB, Delhi.