UNCONVENTIONAL PROTEIN TARGETS OF MULTI DRUG RESISTANT ACINETOBACTER

Abstract

Bacteria can be grouped into two categories as beneficial and harmful. The bacteria which coexist with humans without causing any diseases are known as beneficial. Sometimes, these turn out to be dangerous when they infect people having a compromised immune system, viz. hospitalized patient or person suffering from cancer, HIV or diabetes. Harmful bacteria are the major cause of illness and leading to death in severe cases. Bacterial infections borne diseases are the second leading cause of death worldwide. Primary classification of bacteria is done on the basis of a laboratory test known as Gram-staining. The Gram-stain differentiates bacteria into two types, i.e., Gram-positive and Gram-negative. Gram-negative bacteria would not be able to retain the stain and would appear pink under the microscope; whereas, Gram-positive bacteria would appear purple in colour due to the retention of stain by their cell wall. This happens because of the difference in the composition of their cell walls. The cell wall forms a tight barrier against the outside environment providing immunity to both these bacterial types from different medications as well as host immune responses. Secondary metabolites have been observed to neutralize this defense barrier of bacteria. First effective metabolite discovered against bacterial cell wall was penicillin, and with this discovery it declared the beginning of golden age of antibiotics. Major diseases caused by Gram-negative and Grampositive bacteria are listed in Table 1. The composition of the bacterial cell wall not only affects Gram-staining but also protects the bacteria from various medicines and immune system responses. The cell wall composition differs between Gram-negative and Grampositive bacteria (Figure 1) and in both cases it forms a tight barrier against the outside environment. Few enzymes in the human body are capable of destroying cell wall which results in the death of the bacterium. Some microbial secondary metabolites, for example, penicillin prevents the formation of a water-tight Gram-positive cell wall, which causes the destruction of certain bacteria. The Gram-negative bacteria contain complex cell wall structure which protects the bacterium from immune system attack and prevents many antibiotics from working. Penicillin, a well known fungal secondary metabolite, declared the beginning of the antibiotics. Later, antibiotics are considered as magic bullet to cure various diseases. By the mid-20th century, the golden age of antibiotics provided a bountiful arsenal of tools for the treatment of bacterial infections. Extensive investigations were performed on hundreds of microbial metabolites to control bacterial diseases. Conversely, as Chapter 1 Introduction 2 this era came to a close, widespread resistance to antibiotics by pathogenic bacteria turned into a serious health problem for community; organisms that were once sensitive to these drugs now well survive under the same treatment. The Infectious Diseases Society of America documented those antibiotic-resistant pathogens that are most commonly encountered in the clinic as the ESKAPE pathogens [1, 2]. 1.1.1. ESKAPE pathogens ESKAPE pathogen incorporates both Gram-positive and Gram-negative organisms and includes Enterrococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. These pathogens pose as a potent threat for the patients as they are responsible for the majority of hospital-acquired infections. Furthermore, their pan-resistance for widespread antibiotic therapies has required the use of previously retired techniques having high toxicity [3, 4]. Since decade, advance molecular biology techniques have deciphered to thorough information about individual resistance mechanisms in all these pathogens. Still the data showing the interplay between resistance mechanism and bacteria is not sufficient to understand how the bacteria acquire these mechanisms. In addition, data on the impact of clinical interventions to decrease the prevalence of resistance are also lacking.