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.

Proteases

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.

Prospects

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

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