The Microbial Pathogens

Bacteria are unicellular and are thought to live alone and in isolation. They are perceived to be introverts and arrogant. However, bacterial multiply and live together in large numbers as colonies. They also exist as communities, where diverse bacteria may live together and help each other. However, they have well developed defense mechanisms, which enable them to survive through stress conditions and maintain their integrity. Pathogenic microbes infect human beings and cause a wide range of diseases. The worry of the Health Departments is: How to handle this ever evolving battle between human beings and pathogenic microbes?

Countering Microbial Arsenal

A variety of approaches have been tried to counter microbial attack: (i) the Vaccines, (ii) the Antibiotics, and (iii) the Antipathogens.

The Vaccine Way

Vaccines are biological responses, which enable living beings to acquire immunity against specific diseases. Here, the body is prepared for protecting itself in anticipation of any microbial threat. The microbe â€" killed form or made less or non-virulent stimulates the body’s immune system. These are either prophylactic, which prevents future infectious attacks or therapeutic. Although, vaccines have proved effective in fighting infectious diseases, however, certain limitations exist â€" inadequate immune response, or genetic (lack of B cells to generate antibodies). The vaccines may show adverse effects: fever, pain, muscular cramps, etc. In India, vaccines against polio have proved to be a great success.

The Antibiotic Way

Deadly diseases caused by strains of Clostridium, Yersinia, Streptococcus, and Staphylococcus species have been responsible for the epidemic witnessed in the 18th century. Discovery of antibiotics was a great relief, which brought hope to humanity. Sir Alexander Fleming discovered the wonder drug - the antibiotic â€" penicillin. However, the signs of hope started fading with the emergence of strains of Staphylococcus resistant to penicillin. Later on, Shigella strains resistant to tetracycline, and Streptococcus strains to erythromycin were reported. This provoked medical practitioners to prescribe higher doses of antibiotics. Bacteria reacted to this unwarranted stress and evolved drug resistance. The continuous emergence of antibiotic resistant bacteria discouraged researchers. Soon Pharmaceutical companies also started thinking of dis-investing in this area.

The Antipathogen Way

Bacteria, which cause infectious diseases, are bestowed with certain unique characteristics. At low cell densities, they don’t express genes which will provoke human immune system to get activated. Initially, they maintain a low profile to evade human immune system. They become virulent by expressing genes responsible for pathogenicity, only at high cell densities, a phenomenon termed as quorum sensing (QS). The phenotype, which proves highly effective in protecting bacteria from any attack, is the formation of biofilm. Within the biofilm, bacteria behave like highly antibiotic resistant forms. In comparison to their planktonic counter parts, they may show up to 1000 times more resistance to antibiotics.

In Nature, microbes exploit QS to produce antibiotics and toxins, which have the potential to kill other microbes in their vicinity. These rival organisms produce molecules, which act as QS inhibitors (QSIs). R&D efforts have revealed bacteria like Pseudomonas, Ralstonia, Acinetobacter, Arthrobacter, Comamononas, Tenacibaculum Rhodococcus, Bacillus, Oceanobacillus, and Streptomyces, to produce QSIs. On the other hand, certain plants including legumes and medicinal plants produce secondary metabolites, which act as QSIs. These QSIs can disrupt biofilms and expose bacteria, which then become susceptible to lower doses of antibiotics. These QSIs can thus treat bacterial infections. Since these molecules don’t cause any unnecessary stress on bacterial growth, the risk of their developing resistance to QSIs is quite low.

Among the different molecules, which can act as QSIs, the most attractive are the enzymes: (i) acylhomoserine lactone - lactonase (AHL-lactonase), and (ii) AHL-acylases. These enzymes inactivate the QS signal molecules - acylhomoserine lactones (AHL), which are composed of a lactone ring and a variable carbon (C) length acyl chain. AHL-lactonases act by breaking open the lactone ring of the AHL molecule, where as AHL-acylases act by cleaving the acyl side chain. AHL-lactonases have a greater advantage as they are independent of acyl chain length, where as AHL-acylases are chain length specific.

The best bet

Bacillus is generally regarded as safe organisms. It has a great ability to produce AHL-lactonases. These have been reported to be effective in: (i) protecting fish from pathogenic bacteria such as Vibrio species, and (ii) preventing biofouling of membranes used for treating drinking water, etc.

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