Pseudomonas Aeruginosa and Nosocomial Infections

Bielecki et al. search Paper genus genus genus genus genus Pseudomonas aeruginosa is a negative bacterium, particularly known for ca apply nosocomial infections (1). As a pathogen, it effectively causes unsoundness by acquiring guard to antibiotic drugs that would motleyly inhibit growth (2). Reported evaluate of infection range from 0. 6 to 32% crosswise various clinical environments because Pseudomonas aeruginosa has gained multi-drug granting immunity (2). Certain punctuates of Pseudomonas aeruginosa treated with gamma rays layabout break guttle the hydrocarbons in crude oil and be thus useful in cleaning up oil spills (3).The genome of Pseudomonas aeruginosa is 6. 3 million base pairs long, which is the largest bacterial genome to be epochd (4). It contains about 5,570 open reading frames (4). Argyrin is a naturally synthesized antibiotic peptide extracted from myxobacteria (1). It has cytotoxic properties, suppresses the immune system, and is a highly particip ating antibiotic employ against Pseudomonas agate lines (1). turn 1. Argyrin A structure. Bielecki et al chose to isolate these liberal clones in order to reveal the mechanisms by which the P. eruoginosa acquires opponent to Argyrin A indoors the fusA1 ingredient (1). They isolated these clones by growing Pseudomonas aeruginosa strains on agar that contained Argyrin A (1). after(prenominal) incubation, the colonies that formed were able to grow in the presence of argyrin these colonies were then streaked onto plates with Argyrin A again to ensure accuracy of obtaining broad strains (1). A allude mutation is an novelty of one base pair within a DNA sequence (5). The point mutations, which caused changes in the amino acid sequence within the fusA1 gene, were different among the six isolates (1).They big businessman adjudge conferred resistance because the mutations caused the same strike on the resulting protein (1). The gene was identified by sequencing the whole genom e of Pseudomonas aeruginosa strains with the bacterial fundament of Argyrin A, which showed mutations within fusA1 that encode for the annexe chemical element EF-G in resistant strains of Pseudomonas aeruginosa (1). The draw below illustrates the process of elongation during the translational phase in EF-G along with EF-Tu (12). lick 2. Elongation during ribosome-catalyzed translation (12). Bielecki et al corroborate the identity of the gene by using genetic maps. This required sequencing the resistant strain a second time to limit a reference strain to comp be the genes at a specific loci (1). Adding a mutation into the sensitive Pseudomonas aeruginosa strain demonstrated a resistance phenotype (1). step to the fore plasmon resonance is a lab technique that involves aiming a beam of light at a thin metal opinion poll, which catalyzes a reaction by causing lawsuit in the molecules behind the metal sheet (6).SPR was useful in this experiment because it affirm that fusA1 is the fundament gene for Argyrin A, rather than fusidic acid, the antibiotic previously recognized (1). A heterological protein, or a heterologue, is a protein that differs in structure and function relative to a given protein not all proteins with different amino acid sequence needfully differ in function (7). N-terminal His6-tags were amalgamate to the fusA1 genes before undergoing the SPR experiments, causing the production of heterologic proteins in relation to the original fusA1 (1).According to Bielecki et al, the SPR procedures support that Argyrin A binds to fusA1 by the resulting KD value (1). This shows that Argyrin A has a target on the heterologic protein (1). It is important to compargon the variations made in the mutations because the oppo target bacteria may have a different sequence that can still achieve resistance (1). It cannot be assumed that all bacterial strains exit be identically resistant or sensitive because they all contain differences in their gen omes (1). By mapping the mutated genes, the authors found the locations of the mutations in different plains (1).They deduced that the mutations exhibiting resistance to Argyrin A in Pseudomonas aeruginosa are found on oppo localize sides of the domain, despite the fact that well-nigh mutations involving fusidic acid and Argyrin A are situated on the same side of the domain (1). This shows that the binding sites for fusidic acid and Argyrin A moldiness be independent of each other (1). Both fusA1 and the second gene, fusA2, encode for the elongation part EF-G (1). The fusA2 gene was expressed 30 times less in the strains of Pseudomonas aeruginosa than in the fusA1 gene, as shown by ribonucleic acid sequencing (1).Homology poseing uses the model of a target protein to produce an estimated structure of a homologic template protein (8). After creating a homology model of Argyrin As protein structure, Bielecki et al think that it most likely binds to a site distinct from that of fusidic acid, indicating a new mode of protein biosynthesis inhibition by Argyrin A (11). Multi-drug resistant pathogens pose a precise big risk on the origination because they can easily mutate their genomes to hug resistance to a given antibiotic and persist in causing harmful diseases (1).The authors used MDR clinic isolates in order to observe the mechanisms by which these pathogens mutate to build resistance to Argyrin. The fact that eleven of the twelve isolates showed aesthesia to Argyrin suggests that Argyrin is a useful antibiotic in preventing infections by Pseudomonas aeruginosa (1). There are other factors besides the expenditure and exportation of Argyrin that affect Pseudomonas aeruginosas aesthesia to Argyrin, such as efflux pumps (1) however, the uptake and export of Argyrin in other bacteria does play a role in its sensitivity (9).A proteasome is a hollow protein interlinking with active sites that break down proteins by proteolysis (10). The degraded pepti des that are produced can be used for other functions in the stall (10). Argyrin A is a factor used to inhibit proteasome function, yet there is no distinct evidence that Argyrin A binds to the site on the proteasome (1). This paper is important because it analyzes the resistance and sensitivity to Argyrin A in various strains of Pseudomonas aeruginosa.This bacteria has been a stellar(a) cause in nosocomial infections, so it is important to determine which antibiotics best bestow to stop the spread of disease (1). slightly ten percent of patients in hospitals across the United earths obtain a portentous nosocomial infection (13). Although there are effective methods to prevent the spread of pathogens in clinical environments (13), it is important to study how bacteria acquire resistance, so that scientists can sustain ways to inhibit the spread of nosocomial infections by multi-drug resistant pathogens.Bibliography Bielecki, P. , Lukat, P. , Husecken, K. , Dotsch, A. , Steinm etz, H. , Hartmann, R. W. , Muller, R. , and Houssler, S. (2012) Mutation in elongation factor G confers resistance to the antibiotic Argyrin in the opportunist pathogen Pseudomonas aeruginosa. Chembiochem. 13, 2339-2345. Obritsch, M. D. , Fish, D. N. , MacLaren, R. , and Jung, R. (2005) Nosocomial infections due to multidrug-resistant Pseudomonas aeruginosa epidemiology and intervention options. Pharmacotherapy. 25, 1353-1364. Iqbal, S. , Khalid, Z. M. and Malik, K.A. (1995) Enhanced biodegradation and emulsification of crude oil and hyperproduction of biosurfactants by a gamma ray-induced mutant of Pseudomonas aeruginosa. Lett. Appl. Microbiol. 21,176179. C. K. Stover, X. Q. Pham, A. L. Erwin, S. D. Mizoguchi, P. Warrener, M. J. Hickey, F. S. L. Brinkman, W. O. Hufnagle, D. J. Kowalik, et al. (2000) Complete genome sequence of Pseudomonas aeruginosa PAO1, and opportunistic pathogen. Nature. 406, 959-964. Encyclopedia Britannica Online. Point mutation. Accessed 17 Oct. 2012 http// www. britannica. om/EBchecked/ effect/54744/point-mutation Manfield, I. (2009) Biacore surface plasmon resonance. Univ. of Leeds, Astbury Centre for Structural molecular Biology. Accessed 18 Oct. 2012 http//www. astbury. leeds. ac. uk/facil/SPR/spr_intro2004. htm Jackson, J. H. (1999) Terminologies for gene and protein similarity. Michigan State Univ. , Dept. of Microbiology. Accessed 19 Oct. 2012 https//www. msu. edu/jhjacksn/Reports/similarity. htm Bevan, D. R. (2003) Homology simulation. Virginia Tech, Dept. of Biochemistry. Accessed on 19 Oct. 012 http//www. biochem. vt. edu/modeling/homology. html Sasse, F. , Steinmetz, H. , Schupp, T. , Petersen, F. , Memmert, K. , Hofmann, H. , Heusser, C. , Brinkmann, V. , von Matt, P. , Hofle, G. , and Reichenbach, H. (2002) Argyrins, immunosuppressive cyclic peptides from myxobacteria. I. Production, isolation, physico-chemical and biologic properties. J. Antiobiot. 55, 543-551. Rape, M. , and Jentsch, S. (2002) Taking a bite proteasoma l protein processing. Nat. carrell Biol. 4, 113-116. Bielecki, P. , Lukat, P. , Husecken, K. , Dotsch, A. Steinmetz, H. , Hartmann, R. W. , Muller, R. , and Houssler, S. (2012) Mutation in elongation factor G confers resistance to the antibiotic Argyrin in the opportunistic pathogen Pseudomonas aeruginosa. Chembiochem. 13, 2340. Simonovic, M. and Steitz, T. A. (2009) A geomorphologic view on the mechanism of the ribosome-catalyzed peptide draw formation. BBA Gene Reg. Mech. 1789, 612-623. Abedon, S. T. (2009) Nosocomial infections. Ohio State University. Accessed on 27 Oct. 2012 http//www. mansfield. ohio-state. edu/sabedon/biol2053. htm