Antibiotic resistance innate

Keywords Pseudomonas aeruginosa Cystic fibrosis Lipopolysaccharide Lipid A Chronic infection Antibiotic resistance Innate immunity inflammation... 

MDR transporters are usually encoded by housekeeping genes as normal constituents of bacterial chromosome and are present in the whole population of a given bacterial species. The basal level of expression of nonspecific multidrug efflux pumps in wild-type cells determines the basal level of antibiotic susceptibility. This innate resistance may still be low enough such that bacteria are susceptible to therapy with a given antibiotic. 

An important characteristic of microbial biofilms is their innate resistance to immune system and antibiotic killing (89, 90). This has made microbial biofilms a common and difficult-to-treat cause of medical infections (87,91,92). It has recently been estimated that over 60% of the bacterial infections currently treated in hospitals are caused by bacterial biofilms (91). Several ehronic infections (e.g. respiratory infections caused by Pseudomonas aeruginosa in the cystic fibrosis lung. Staphylococcal lesions in endocarditis, and bacterial prostatitis, primarily caused by Escherichia coli) have been shown to be mediated by biofilms (93). More notably, biofilms (particularly of Staphylococcus aureus, P. aeruginosa, and E. coli) are also a major cause of infections associated with medical implants (94, 95). The number of implant-associated infections approaches 1 million per year in the United States alone, and their direct medical costs exceed 3 billion annually (96). Thus, there is an urgent need to find novel approaches to eradicate biofilms. 

Peptides are also amphiphilic polymers, i.e., mostly positively charged molecules with short amino acid chains, and are a key component of the innate immune system. The focus on amphiphilic polymers is due to some reports suggesting that the current global drug pipeline is woefully inadequate due to bacterial resistance to antibiotics [3]. The application of amphiphilic polymers and their block polymers to stop the microbial growth of infected tissue has been reported in the literature [4]. 

The mechanisms of resistance to biocides are relatively poorly understood in comparison with antibiotics. Bacterial resistance to antibiotics is normally considered to be of two types (a) intrinsic (innate, natural), a natural property of the organism, or (b) acquired, either by chromosomal mutation or by the acquisition of extraneous DNA, usually acquired as plasmids or transposons [53, 236, 237]. 

Antimicrobial resistance traits are genetically coded and can either be intrinsic or acquired. Intrinsic resistance is due to innately coded genes which create natural insensitivity to a particular antibiotic. Innate resistance is normally expressed by virtually all strains of that particular bacterial species. Acquired resistance is gained by previously susceptible bacteria either through mutation or horizontally obtained from other bacteria possessing such resistance via transformation, transduction, or conjugation. Acquired resistance is limited to subpopulations of a particular bacterial species and may result from selective pressure exerted by antibiotic usage. 

Collins, B., Curtis, N., Cotter, P.D., et al. (2010). The ABC transporter AnrAB contributes to the innate resistance of Listeria monocytogenes to nisin, bacitracin, and various beta-lactam antibiotics. Antimicrob Agents Chemother 54, 4416-4423. 

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