Innate resistance

Intrinsic (natural, innate) resistance. In one form of intrinsic resistance, the fungal cell wall (see Chapter 2) is considered to present a barrier to exclude or, more likely, to reduce the penetration by biocide molecules. The evidence to date is sketchy but the available information tentatively links cell wall glucan, wall thickness and consequent relative porosity to the sensitivity of Saccharomyces cerevisiae to chlorhexidine. 

Table 11.3 Selected microorganisms toward which innate resistance in the mouse is governed by the Nrampl gene.

Unlike fungal saponinases, little is known about hydrolytic enzymes secreted by phytopathogenic oomycetes or their role in pathogenicity [75, 76]. Although innate resistance is believed to be the main mechanism by which oomycetes avoid the toxicity of saponins (see above), some oomycetes have been found to produce saponin hydrolases [77], as well as other glycosyl hydrolases [76]. 

By the time they have reached the lungs, schistosomula are innately resistant to immune effector mechanisms that are capable of killing schistosomula newly transformed from cer-cariae. In part, this is a reflection of the fact that growing schistosomula develop the ability to avoid activating complement and to evade recognition by antibodies (see below), and therefore are no longer susceptible to antibody or complement-mediated cellular cytotoxicity. However, studies in which these evasion mechanisms have been experimentally bypassed have revealed underlying resistance to immune effector molecules (Moser et al., 1980) the basis of this resistance is unknown. 

Trinchieri, G. (2003) Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nature Reviews in Immunology 3, 133-146. 

Naturally resistant strains. Some bacteria are innately resistant to certain classes of antimicrobial agent, e.g. coliforms and many other Gramnegative bacteria possess outer cell membranes which protect their cell walls from the action of certain penicillins and cephalosporins. Facultatively anaerobic bacteria (such as Escherichia colt) lack the ability to reduce the nitro group of metronidazole which therefore remains in an inactive form. In the course of therapy, naturally sensitive organisms are eliminated and those naturally resistant proliferate and occupy the biological space newly created by the drug. 

Microorganisms vary tremendously in their susceptibility to chemical disinfectants. Prions, bacterial endospores and mycobacteria possess the most innate resistance, while many vegetative bacteria and some viruses appear highly susceptible (see Chapter 17). In addition, microorganisms adhering to surfaces as biofilms or present within other cells (e.g. legionellae within amoebae), may reveal a marked... 

Some bacteria are said to have innate resistance... 

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. 

Microbial resistance to drugs can emerge via the gradual selecting out of innately resistant mutant strains from a microbial population or, more commonly, via R-factor plasmid-mediated transmission between bacteria. The primary mechanisms of microbial resistance are shown in Table V-1-2. 

Aminoglycosides are bactericidal, accumulated intracellularly in microorganisms via an independent uptake thus, anaerobes are innately resistant. 

With innate resistance an entire bacterial species or a certain percentage of a population are naturally resistant to a drug. For example. Pseudomonas aeruginosa has always been resistant to flucloxacillin. 

Trinchieri G. Interleukin-12 a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Ann Rev Immunol 1995 13 251-276. 

Gosselin D, DeSanctis J, Boule M, Skamene E, Matouk C, Radzioch D. Role of tumor necrosis factor alpha in innate resistance to mouse pulmonary infection with Pseudomonas aeruginosa. Infect Immun 1995 63(9) 3272-3278. 

Bancroft GJ, Kelly JP. Macrophage activation and innate resistance to infection in SCID mice. Immunobiology 1994 191 424 31. 

Bender B, Georgel P, Rutschmann S et al 2005 Genetic analysis of innate resistance to mouse cytomegalovirus (MCMV). Brief Funct Genomic Proteomic 4 203—213 Carninci P, Kasukawa T, Katayama S et al 2005 The transcriptional landscape of the mammalian genome. Science 309 1559—1563... 

Karupiah G, Chen JH, Nathan CF, Mahalingam S, MacMickingJD 1998 Identification of nitric oxide synthase 2 as an innate resistance locus against ectromeHa virus infection. J Virol 72 7703-7706... 

In this scenario, neutrophils modulate the balance between humoral and cell-mediated immunity and are engaged in a complex cross talk with immune and endothelial cells that bridge innate resistance and adaptive immunity. 

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. 

Davis-Poynter NJ, Farrell HE (1997) Human and murine cytomegalovirus evasion of cytotoxic T lymphocyte and Natural Killer cell-mediated immune responses. Semin Virol 8 369-376 Delano ML, Brownstein DG (1995) Innate resistance to lethal mousepox is genetically linked to the NK gene complex on chromosome 6 and correlates with early restriction of virus replication by cells with an NK phenotype. J Virol 69 5875-5877... 

Straussman R, Morikawa T, Shee K, Batzily-Rokni M, Qian ZR, Du J, Davis A, Mongare MM, Gould J, Frederick DT, Cooper ZA, Chapman PB, Solit DB, Ribas A, Lo RS, Flaherty KT, Ogino S, Wargo JA. Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature. 2012 487 500-4. 

Two major types of microbial resistance can be distinguished intrinsic and acquired resistance. Intrinsic (innate) resistance refers to a natural chromosomally controlled property, including physiological adaptation. 

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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