Main Article Content
Acinetobacter baumannii (A. baumannii) is a major opportunistic nosocomial pathogen, mostly resistant to several groups of antibiotics. Colistin is now used as a last-line treatment for isolates that are highly resistant. The purpose of this study is to identify the importance of LptD; which is involved in the translocation of LPS from the inner membrane to the outer membrane in compartment with LptA and LptC of A. baumannii and its indispensable role as a virulence factor, and the efficiency of colistin as a monotherapy. In the current research, two isolates of A.baumannii were used, the local isolate HHR1 isolated from urine sample and the global strain ATCC 17904, and three antibiotics (colistin, rifampicin and Fosfomycin) were used as a monotherapy and synergic therapy in vivo and ex vivo. The results demonstrated that A. baumannii HHR1 was more resistant to Antimicrobial peptides (AMPs) than the standard strains. The effect of AMPs on A. baumannii was increased by increasing the concentration and the time of incubation, and also AMPs were shown to be lethal on A. baumannii growth spatially at high concentration (2 µg ml-1) in monotherapy and (1.5, 2 µg ml-1) in synergic. The susceptibility of isolates towards antibiotics was variable, where colistin exerts significant growth had defect as a monotherapy and in combination with others. The results showed that the expression of lptD, lptA genes of A.baumannii HHR1 were higher than of the same genes in A.baumannii ATCC 17904 in the presence of 2 µg ml-1 colistin, while lptE gene of the A.baumannii ATCC 17904 showed an upregulation pattern than in A.baumannii HHR1. Furthermore, colistin influences the adhesion ability of A. baumannii on epithelial cells (A-549 lung cancer cell) by reducing the number of cells, and thus could colistin be a good candidate for A. baunmannii treatment.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Al-Haideri HH. Gene Expression of blaOXA-51-like and blaOXA-23 in response to β-Lactam antibiotic in clinically isolates Acinetobacter baumanii and Acinetobacter lowffii from urine samples. Iraqi J Agric Sci. 2019;50(4).
Rebic V, Masic N, Teskeredzic S, Aljicevic M, Abduzaimovic A, Rebic D. The importance of acinetobacter species in the hospital environment. Med Arch. 2018;72(5):325.
Van Duin D, Paterson DL. Multidrug-resistant bacteria in the community: trends and lessons learned. Infectious Disease Clinics. 2016 Jun 1;30(2):377-90.
Xu L, Shao C, Li G, Shan A, Chou S, Wang J, Ma Q, Dong N. Conversion of broad-spectrum antimicrobial peptides into species-specific antimicrobials capable of precisely targeting pathogenic bacteria. Sci. Rep. 2020 Jan 22;10(1):1-9. اختصار اسم المجلة
Zanetti M. Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol. 2004;75(1):39–48.
Lei J, Sun L, Huang S, Zhu C, Li P, He J, et al. The antimicrobial peptides and their potential clinical applications. Am J Transl Res. 2019;11(7):3919.
Dong H, Zhang Z, Tang X, Paterson NG, Dong C. Structural and functional insights into the lipopolysaccharide ABC transporter LptB 2 FG. Nat Commun. 2017;8(1):1–11.
Janssen AB, Bartholomew TL, Marciszewska NP, Bonten MJ, Willems RJ, Bengoechea JA, et al. Nonclonal Emergence of Colistin Resistance Associated with Mutations in the BasRS Two-Component System in Escherichia coli Bloodstream Isolates. Msphere. 2020 Apr 29;5(2).
Bialvaei AZ, Samadi Kafil H. Colistin, mechanisms and prevalence of resistance. Curr Med Res Opin. 2015;31(4):707–21.
Biswas S, Brunel J-M, Dubus J-C, Reynaud-Gaubert M, Rolain J-M. Colistin: an update on the antibiotic of the 21st century. Expert Rev Anti Infect Ther. 2012;10(8):917–34.
Li Z, Cao Y, Yi L, Liu JH, Yang Q. Emergent polymyxin resistance: end of an era?. InOpen forum infectious diseases 2019 Oct (Vol. 6, No. 10, p. ofz368). US: Oxford University Press.
Bialvaei AZ, Kafil HS, Asgharzadeh M, Yousef Memar M, Yousefi M. Current methods for the identification of carbapenemases. J Chemother. 2016;28(1):1–19.
Lee HJ, Bergen PJ, Bulitta JB, Tsuji B, Forrest A, Nation RL, et al. Synergistic activity of colistin and rifampin combination against multidrug-resistant Acinetobacter baumannii in an in vitro pharmacokinetic/pharmacodynamic model. Antimicrob Agents Chemother. 2013;57(8):3738–45.
Leelasupasri S, Santimaleeworagun W, Jitwasinkul T. Antimicrobial susceptibility among colistin, sulbactam, and fosfomycin and a synergism study of colistin in combination with sulbactam or fosfomycin against clinical isolates of carbapenem-resistant Acinetobacter baumannii. J Pathog. 2018;2018.
Hamzah AS. Genetic Variations in rplB Gene Associated with Multidrug Resistance Acinetobacter baumannii Isolated from Different Clinical Sources. Al-Nahrain J Sci. 2018;21(3):119–25.
Al-Haideri H. Characterization of novel proteins in the cell envelope of Campylobacter jejuni A thesis submitted in part fulfilment for the degree of Doctor of Philosophy. Department of Molecular Biology and Biotechnology, The University of Sheffield. 2015;(March).
Kadhim WKA, Nayef UM, Jabir MS. Polyethylene glycol-functionalized magnetic (Fe3O4) nanoparticles: A good method for a successful antibacterial therapeutic agent via damage DNA molecule. Surf Rev Lett. 2019;26(10):1–15.
Al-Shammari AM, Alshami MA, Umran MA, Almukhtar AA, Yaseen NY, Raad K, et al. Establishment and characterization of a receptor-negative, hormone-nonresponsive breast cancer cell line from an Iraqi patient. Breast Cancer Targets Ther. 2015;7:223.
Aghapour Z, Gholizadeh P, Ganbarov K, Bialvaei AZ, Mahmood SS, Tanomand A, et al. Molecular mechanisms related to colistin resistance in Enterobacteriaceae. Infect Drug Resist. 2019;12:965.
Li J, Rayner CR, Nation RL, Owen RJ, Spelman D, Tan KE, et al. Heteroresistance to colistin in multidrug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother. 2006;50(9):2946–50.
Hernan RC, Karina B, Gabriela G, Marcela N, Carlos V, Angela F. Selection of colistin-resistant Acinetobacter baumannii isolates in postneurosurgical meningitis in an intensive care unit with high presence of heteroresistance to colistin. Diagn Microbiol Infect Dis. 2009;65(2):188–91.
Tan C-H, Li J, Nation RL. Activity of colistin against heteroresistant Acinetobacter baumannii and emergence of resistance in an in vitro pharmacokinetic/pharmacodynamic model. Antimicrob Agents Chemother. 2007;51(9):3413–5.
Yu X-H, Song X-J, Cai Y, Liang B-B, Lin D-F, Wang R. In vitro activity of two old antibiotics against clinical isolates of methicillin-resistant Staphylococcus aureus. J Antibiot (Tokyo). 2010;63(11):657–9.
Bai Y, Liu B, Wang T, Cai Y, Liang B, Wang R, et al. In vitro activities of combinations of rifampin with other antimicrobials against multidrug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother. 2015 Mar 1;59(3):1466-71.
Vázquez-López R, Solano-Gálvez SG, Juárez Vignon-Whaley JJ, Abello Vaamonde JA, Padró Alonzo LA, Rivera Reséndiz A, et al. Acinetobacter baumannii Resistance: A Real Challenge for Clinicians. Antibiotics. 2020 Apr;9(4):205.
Asif M, Alvi IA, Rehman SU. Insight into Acinetobacter baumannii: pathogenesis, global resistance, mechanisms of resistance, treatment options, and alternative modalities. Infect. and drug resist. 2018;11:1249.
Krishnamurthy M, Lemmon MM, Falcinelli EM, Sandy RA, Dootz JN, Mott TM, et al. Enhancing the antibacterial activity of polymyxins using a nonantibiotic drug. Infec. and Drug Resis.. 2019;12:1393.
Kheshti R, Pourabbas B, Mosayebi M, Vazin A. In vitro activity of colistin in combination with various antimicrobials against Acinetobacter baumannii species, a report from South Iran. Infec. and Drug Resist.. 2019;12:129.
Giannouli M, Di Popolo A, Durante-Mangoni E, Bernardo M, Cuccurullo S, Amato G, et al. Molecular epidemiology and mechanisms of rifampicin resistance in Acinetobacter baumannii isolates from Italy. Int J Antimicrob Agents. 2012;39(1):58–63.
Cheah S-E, Li J, Tsuji BT, Forrest A, Bulitta JB, Nation RL. Colistin and polymyxin B dosage regimens against Acinetobacter baumannii: differences in activity and the emergence of resistance. Antimicrob Agents Chemother. 2016;60(7):3921–33.
Rigatto MH, Oliveira MS, Perdigão-Neto L V, Levin AS, Carrilho CM, Tanita MT, et al. Multicenter prospective cohort study of renal failure in patients treated with colistin versus polymyxin B. Antimicrob Agents Chemother. 2016;60(4):2443–9.
Parker SL, Frantzeskaki F, Wallis SC, Diakaki C, Giamarellou H, Koulenti D, et al. Population pharmacokinetics of fosfomycin in critically ill patients. Antimicrob Agents Chemother. 2015;59(10):6471–6.
Nastro M, Rodríguez CH, Monge R, Zintgraff J, Neira L, Rebollo M, et al. Activity of the colistin–rifampicin combination against colistin-resistant, carbapenemase-producing Gram-negative bacteria. J Chemother. 2014;26(4):211–6.
Poirel L, Jayol A, Nordmann P. Polymyxins: antibacterial activity, susceptibility testing, and resistance mechanisms encoded by plasmids or chromosomes. Clin Microbiol Rev. 2017 Apr 1;30(2):557-96.
Wehrli W. Rifampin: mechanisms of action and resistance. Rev Infect Dis. 1983;5(Supplement_3):S407–11.
Hancock REW, Chapple DS. Peptide antibiotics. Antimicrob Agents Chemother. 1999;43(6):1317–23.
Cafiso V, Stracquadanio S, Lo Verde F, Gabriele G, Mezzatesta ML, Caio C, et al. Colistin resistant Acinetobacter. baumannii: genomic and transcriptomic traits acquired under colistin therapy. Front Microbiol . 2019 Jan 7;9:3195.
Henry R, Vithanage N, Harrison P, Seemann T, Coutts S, Moffatt JH, et al. Colistin-resistant, lipopolysaccharide-deficient Acinetobacter baumannii responds to lipopolysaccharide loss through increased expression of genes involved in the synthesis and transport of lipoproteins, phospholipids, and poly-β-1, 6-N-acetylglucosamine. Antimicrob Agents Chemother. 2012;56(1):59–69.
Ko KS, Suh JY, Kwon KT, Jung S-I, Park K-H, Kang CI, et al. High rates of resistance to colistin and polymyxin B in subgroups of Acinetobacter baumannii isolates from Korea. J Antimicrob Chemother. 2007;60(5):1163–7.
Park YJ, Hong DJ, Yoon EJ, Kim D, Choi MH, Hong JS, et al. Differences in Colistin-resistant Acinetobacter baumannii Clinical Isolates Between Patients With and Without Prior Colistin Treatment. Annals of laboratory medicine. 2018 Nov;38(6):545-54.
Adams MD, Nickel GC, Bajaksouzian S, Lavender H, Murthy AR, Jacobs MR, et al. Resistance to colistin in Acinetobacter baumannii associated with mutations in the PmrAB two-component system. Antimicrob Agents Chemother. 2009;53(9):3628–34.
López-Rojas R, Jiménez-Mejías ME, Lepe JA, Pachón J. Acinetobacter baumannii resistant to colistin alters its antibiotic resistance profile: a case report from Spain. J Infect Dis. 2011;204(7):1147–8.
Vrancianu CO, Pelcaru CF, Alistar A, Gheorghe I, Marutescu L, Popa M, et al. Escaping from ESKAPE. Clinical Significance and Antibiotic Resistance Mechanisms in Acinetobacter baumannii: a Review. Biointerface Research in Applied Chemistry.Biointerface Reserch in Applied chemistry. 2020 jul 11(1),8190-8203.
Hood MI, Jacobs AC, Sayood K, Dunman PM, Skaar EP. Acinetobacter baumannii increases tolerance to antibiotics in response to monovalent cations. Antimicrob Agents Chemother. 2010;54(3):1029–41.
He X, Lu F, Yuan F, Jiang D, Zhao P, Zhu J, et al. Biofilm formation caused by clinical Acinetobacter baumannii isolates is associated with overexpression of the AdeFGH efflux pump. Antimicrob Agents Chemother. 2015;59(8):4817–25.
Bojkovic J, Richie DL, Six DA, Rath CM, Sawyer WS, Hu Q, et al. Characterization of an Acinetobacter baumannii lptD deletion strain: permeability defects and response to inhibition of lipopolysaccharide and fatty acid biosynthesis. J Bacteriol. 2016;198(4):731–41.
Whitfield C, Trent MS. Biosynthesis and export of bacterial lipopolysaccharides. Annu Rev Biochem. 2014;83:99–128.
Nhu NTK, Riordan DW, Nhu TDH, Thanh DP, Thwaites G, Lan NPH, et al. The induction and identification of novel Colistin resistance mutations in Acinetobacter baumannii and their implications. Sci Rep. 2016;6(1):1–8.
El-Sayed Ahmed MAE-G, Zhong L-L, Shen C, Yang Y, Doi Y, Tian G-B. Colistin and its role in the Era of antibiotic resistance: an extended review (2000–2019). Emerg Microbes Infect. 2020;9(1):868–85.
Zhang G, Baidin V, Pahil KS, Moison E, Tomasek D, Ramadoss NS, et al. Cell-based screen for discovering lipopolysaccharide biogenesis inhibitors. Proc Natl Acad Sci. 2018;115(26):6834–9.
Longo F, Vuotto C, Donelli G. Biofilm formation in Acinetobacter baumannii. New Microbiol. 2014;37(2):119–27.
Pérez A, Merino M, Rumbo-Feal S, Álvarez-Fraga L, Vallejo JA, Beceiro A, et al. The FhaB/FhaC two-partner secretion system is involved in adhesion of Acinetobacter baumannii AbH12O-A2 strain. Virulence. 2017;8(6):959–74.
Schweppe DK, Harding C, Chavez JD, Wu X, Ramage E, Singh PK, et al. Host-microbe protein interactions during bacterial infection. Chem Biol. 2015;22(11):1521–30.
Nie D, Hu Y, Chen Z, Li M, Hou Z, Luo X, et al. Outer membrane protein A (OmpA) as a potential therapeutic target for Acinetobacter baumannii infection. Int J Biomed Sc. 2020 Dec 1;27(1):26.
Berghmans T, Sculier J-P, Klastersky J. A prospective study of infections in lung cancer patients admitted to the hospital. Chest. 2003;124(1):114–20.
Pietrocola G, Arciola CR, Rindi S, Di Poto A, Missineo A, Montanaro L, et al. Toll-like receptors (TLRs) in innate immune defense against Staphylococcus aureus. Int J Artif Organs. 2011;34(9):799–810.
Chattopadhyay S, Veleeparambil M, Poddar D, Abdulkhalek S, Bandyopadhyay SK, Fensterl V, et al. EGFR kinase activity is required for TLR4 signaling and the septic shock response. EMBO Rep. 2015;16(11):1535–47.
Hattar K, Savai R, Subtil FSB, Wilhelm J, Schmall A, Lang DS, et al. Endotoxin induces proliferation of NSCLC in vitro and in vivo: role of COX-2 and EGFR activation. Cancer Immunol Immunother. 2013;62(2):309–20.
Malaise EP, Fertil B, Chavaudra N, Guichard M. Distribution of radiation sensitivities for human tumor cells of specific histological types: comparison of in vitro to in vivo data. Int J Radiat Oncol Biol Phys. 1986;12(4):617–24.
Krause M, Dubrovska A, Linge A, Baumann M. Radioresistance, prediction of radiotherapy outcome and specific targets for combined treatments. Adv Drug Deliv Rev. 2017;109:63–73.