Persistencia bacteriana: un fenotipo celular de importancia clínica en infecciones crónicas y recurrentes

Autores/as

DOI:

https://doi.org/10.24265/horizmed.2020.v20n1.11

Palabras clave:

Sistemas toxina-antitoxina, Biopelículas, Farmacorresistencia bacteriana

Resumen

Los persistentes bacterianos son variantes transitorias de una población genéticamente homogénea, generada por exposición al estrés, como el que ocurre durante el tratamiento antibiótico. Es un fenómeno epigenético o un fenotipo no heredado, que puede ser llamado primera línea de defensa antes de que se adquiera la resistencia antimicrobiana. A pesar de su descubrimiento hace más de 70 años, su definición, mecanismos de formación, clasificación y morfologías adoptadas de implicancia clínica son temas de investigación actual. En el presente estudio se describe la relación de persistentes con infecciones crónicas y formación de biopelículas como factores importantes en la recaída, recidivas y mayor virulencia en las infecciones. Así mismo, se hace una revisión breve de los diversos mecanismos implicados en la persistencia bacteriana y su eliminación ineficaz por tolerancia antibiótica para terminar con la presentación de posibles estrategias de tratamiento. En conjunto, se cree que la persistencia impone una carga significativa de atención en salud pública, que se estima, provocará hasta 10 millones de víctimas al año para el 2050. Una mejor comprensión de este fenotipo es fundamental en la lucha contra las bacterias patógenas con la finalidad de obtener una mejor perspectiva en las terapias futuras.

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Lewis K. Riddle of biofilm resistance. Antimicrob Agents Chemother. 2001 Apr;45(4): 999–1007.

Balaban NQ, Merrin J, Chait R, Kowalik L, Leibler S. Bacterial persistence as a phenotypic switch. Science. 2004 Sep 10; 305(5690): 1622–5.

Fisher RA, Gollan B, Helaine S. Persistent bacterial infections and persister cells. Nat Rev Microbiol. 2017 Aug; 15 (8): 453–64.

Cui P, Xu T, Zhang WH, Zhang Y. Molecular mechanisms of bacterial persistence and phenotypic antibiotic resistance. Yi Chuan. 2016 Oct 20; 38 (10): 859–71.

Möker N, Dean CR, Tao J. Pseudomonas aeruginosa increases formation of multidrug-tolerant persister cells in response to quorum-sensing signaling molecules. J Bacteriol. 2010 Apr; 192 (7): 1946–55.

Kussell E, Kishony R, Balaban NQ, Leibler S. Bacterial persistence: a model of survival in changing environments. Genetics. 2005 Apr; 169 (4): 1807–14.

Dhar N, McKinney JD. Microbial phenotypic heterogeneity and antibiotic tolerance. Curr Opin Microbiol. 2007 Feb; 10 (1): 30–8.

Fauvart M, De Groote VN, Michiels J. Role of persister cells in chronic infections: clinical relevance and perspectives on anti-persister therapies. J Med Microbiol. 2011 Jun; 60 (6): 699–709.

Hobby GL, Meyer K, Chaffee E. Observations on the Mechanism of Action of Penicillin. Proc Soc Exp Biol Med. 1942 Jun 1; 50 (2): 281–5.

Bigger JW. Treatment of Staphylococcal Infections with Penicillin by Intermittent Sterilisation. The Lancet. 1944 Oct 14:244(6320);497–500.

Van Den Bergh B, Fauvart M, Michiels J. Formation, physiology, ecology, evolution and clinical importance of bacterial persisters. FEMS Microbiol Rev. 2017 May 1; 41 (3): 219–51.

Lewis K. Persister Cells. Annu Rev Microbiol.2010; 64 (1): 357–72.

Chain E, Duthie ES. Bactericidal and bacteriolytic action of penicillin on the Staphylococcus. The Lancet. 1945 May 26; 245 (6352): 652–7.

Amato SM, Fazen CH, Henry TC, Mok WWK, Orman MA, Sandvik EL, et al. The role of metabolism in bacterial persistence. Front Microbiol. 2014 Mar 3; 5 (70): 70.

Moyed HS, Bertrand KP. hipA, a newly recognized gene of Escherichia coli K-12 that affects frequency of persistence after inhibition of murein synthesis. J Bacteriol. 1983 Aug; 155 (2): 768–75.

Jayaraman R. Bacterial persistence: some new insights into an old phenomenon. J Biosci. 2008 Dec; 33 (5): 795–805.

Wood TK, Knabel SJ, Kwan BW. Bacterial persister cell formation and dormancy. Appl Environ Microbiol. 2013 Dec; 79 (23): 7116–21.

O’Neill J. Tackling a global health crisis: initial steps. The Review on Antimicrobial Resistance. 2015 Feb. p 1-22.

Van den Bergh B, Michiels JE, Wenseleers T, Windels EM, Boer PV, Kestemont D, et al. Frequency of antibiotic application drives rapid evolutionary adaptation of Escherichia coli persistence. Nat Microbiol. 2016 Mar 07; 1 (5): 1–7.

Zhang Y. Persisters, persistent infections and the Yin-Yang model. Emerg Microbes Infect. 2014 Jan; 3 (1): 1–10.

Goneau LW, Yeoh NS, MacDonald KW, Cadieux PA, Burton JP, Razvi H, et al. Selective target inactivation rather than global metabolic dormancy causes antibiotic tolerance in uropathogens. Antimicrob Agents Chemother. 2014; 58 (4): 2089–97.

Wang T, El Meouche I, Dunlop MJ. Bacterial persistence induced by salicylate via reactive oxygen species. Sci Rep. 2017; 7 (43839): 1–7.

Helaine S, Kugelberg E. Bacterial persisters: formation, eradication, and experimental systems. Trends Microbiol. 2014 Jul; 22 (7): 417–24.

Xu T, Wang XY, Cui P, Zhang YM, Zhang WH, Zhang Y. The Agr quorum sensing system represses persister formation through regulation of phenol soluble modulins in Staphylococcus aureus. Front Microbiol. 2017 Nov 7; 8 (2189): 1–13.

Patricelli P, Ramirez E, Presa RC, Dell’Elce A, Formentini E. Efecto de la persistencia bacteriana sobre la eficacia de la enrofloxacina y ciprofloxacina frente a una cepa de Escherichia coli. FAVE- Ciencias Vet. 2017 Jun;16 (2017): 30–8.

Maisonneuve E, Gerdes K. Molecular mechanisms underlying bacterial persisters. Cell. 2014 Apr 24; 157 (3): 539–48.

Kim JS, Wood TK. Tolerant, growing cells from nutrient shifts are not persister cells. MBio. 2017 Mar-Apr; 8 (2): e 00354-17

Kwan BW, Valenta JA, Benedik MJ, Wood TK. Arrested protein synthesis increases persister-like cell formation. Antimicrob Agents Chemother. 2013 Mar; 57 (3): 1468–73.

Kaldalu N, Hauryliuk V, Tenson T. Persisters-as elusive as ever. Appl Microbiol Biotechnol. 2016 Aug; 100 (15): 6545–53.

Lebeaux D, Ghigo JM, Beloin C. Biofilm-related infections: bridging the gap between clinical management and fundamental aspects of recalcitrance toward antibiotics. Microbiol Mol Biol Rev. 2014 Sep; 78 (3): 510–43.

Orman MA, Brynildsen MP. Dormancy is not necessary or sufficient for bacterial persistence. Antimicrob Agents Chemother. 2013 Jul; 57 (7): 3230–9.

Trastoy R, Manso T, Fernández-García L, Blasco L, Ambroa A, Pérez del Molino ML, et al. Mechanisms of bacterial tolerance and persistence in the gastrointestinal and respiratory environments. Clin Microbiol Rev. 2018 Aug 1; 31 (4): e 00023-18

Torrey HL, Keren I, Via LE, Lee JS, Lewis K. High persister mutants in Mycobacterium tuberculosis. PLoS One. 2016 May 13;11(5):1–28.

Dörr T, Vulić M, Lewis K. Ciprofloxacin causes persister formation by inducing the TisB toxin in Escherichia coli. PLoS Biol. 2010 Feb; 8 (2): 29–35.

Kim JS, Wood TK. Persistent persister misperceptions. Front Microbiol. 2016; 7 (2134): 1–7.

Singh R, Ray P, Das A, Sharma M. Role of persisters and small-colony variants in antibiotic resistance of planktonic and biofilm-associated Staphylococcus aureus: an in vitro study. J Med Microbiol. 2009 Aug; 58 (8): 1067–73.

Zhang Y, Yew WW, Barer MR. Targeting persisters for tuberculosis control. Antimicrob Agents Chemother. 2012 May; 56 (5): 2223–30.

Pu Y, Zhao Z, Li Y, Zou J, Ma Q, Zhao Y, et al. Enhanced efflux activity facilitates drug tolerance in dormant bacterial cells. Mol Cell. 2016 Apr; 62 (2): 284–94.

Prax M, Bertram R. Metabolic aspects of bacterial persisters. Front Cell Infect Microbiol. 2014; 4 (148): 1–6.

Glover WA, Yang Y, Zhang Y. Insights into the molecular basis of L-form formation and survival in Escherichia coli. PLoS One. 2009 Oct 6; 4 (10): e 7316. W, Xu X, Wang S, Zhang S, et al. Glycerol uptake is important for L-form formation and persistence in Staphylococcus aur

Han J, He L, Shieus. PLoS One. 2014 Sep 24; 9 (9): e 108325.

Yamaguchi Y, Inouye M. Regulation of growth and death in Escherichia coli by toxin-antitoxin systems. Nat Rev Microbiol. 2011 Sep 19; 9 (11): 779–90.

Ramage HR, Connolly LE, Cox JS. Comprehensive functional analysis of Mycobacterium tuberculosis toxin-antitoxin systems: implications for pathogenesis, stress responses, and evolution. PLoS Genet. 2009 Dec; 5 (12): e 1000767.

Fasani RA, Savageau MA. Molecular mechanisms of multiple toxin-antitoxin systems are coordinated to govern the persister phenotype. Proc Natl Acad Sci. 2013 Jun; 110 (27): e 2528–37.

Schumacher MA, Piro KM, Xu W, Hansen S, Lewis K, Brennan RG. Molecular Mechanisms of HipA-Mediated Multidrug Tolerance and Its Neutralization by HipB. Science. 2009 Jan 16; 323 (5912): 396–401.

Korch SB, Henderson TA, Hill TM. Characterization of the hipA7 allele of Escherichia coli and evidence that high persistence is governed by (p)ppGpp synthesis. Mol Microbiol. 2003 Nov; 50 (4): 1199–213.

Harms A, Stanger FV, Scheu PD, de Jong IG, Goepfert A, Glatter T, et al. Adenylylation of Gyrase and Topo IV by FicT Toxins Disrupts Bacterial DNA Topology. Cell Rep. 2015 Sep; 12 (9): 1497–507.

Helaine S, Cheverton AM, Watson KG, Faure LM, Matthews SA, Holden DW. Internalization of Salmonella by macrophages induces formation of nonreplicating persisters. Science. 2014 Jan; 343 (6167): 204–8.

Wagner EG, Unoson C. The toxin-antitoxin system TisB-IstR1: Expression, regulation and biological role in persister phenotypes. RNA Biol. 2012 Dec; 9 (12): 1513–9.

Marquina Díaz D, Santos de la Sen A. Sistemas de quorum sensing en bacterias. Reduca (Biología) Ser Microbiol. 2010; 3 (5): 39–55.

Barreto AC. Quorum Sensing: Sistemas de comunicación bacteriana. Cienc Actual. 2013; 2 (1): 43–50.

Fuqua WC, Winans SC, Greenberg EP. Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators. J Bacteriol. 1994 Jan; 176 (2): 269–75.

Ng WL, Bassler BL. Bacterial quorum-sensing network architectures. Annu Rev Genet. 2009; 43:197–222.

Nealson KH, Hastings JW. Bacterial bioluminescence: its control and ecological significance. Microbiol Rev. 1979 Dec; 43 (4): 496-518.

Schertzer JW, Boulette ML, Whiteley M. More than a signal: non-signaling properties of quorum sensing molecules. Trends Microbiol. 2009 May; 17 (5): 189–95.

Que YA, Hazan R, Strobel B, Maura D, He J, Kesarwani M, et al. A quorum sensing small volatile molecule promotes antibiotic tolerance in bacteria. PLoS One. 2013 Dec 19; 8 (12): e 80140.

Vega NM, Allison KR, Khalil AS, Collins JJ. Signaling-mediated bacterial persister formation. Nat Chem Biol. 2012 Mar; 8 (5): 431–3.

Potrykus K, Cashel M. (p)ppGpp: still magical? Annu Rev Microbiol. 2008 Oct 13; 62: 35–51.

Liu K, Bittner AN, Wang JD. Diversity in (p)ppGpp metabolism and effectors. Curr Opin Microbiol. 2015 Apr; 24: 72-9.

Liu H, Xiao Y, Nie H, Huang Q, Chen W. Influence of (p)ppGpp on biofilm regulation in Pseudomonas putida KT2440. Microbiol Res. 2017 Nov; 204: 1–8.

Vogt SL, Green C, Stevens KM, Day B, Erickson DL, Woods DE, et al. The Stringent Response Is Essential for Pseudomonas aeruginosa Virulence in the Rat Lung Agar Bead and Drosophila melanogaster Feeding Models of Infection. Infect Inmmun. 2011 Oct; 79 (10): 4094-104.

Syal K, Chatterji D. Differential binding of ppGpp and pppGpp to E. coli RNA polymerase: photo-labeling and mass spectral studies Genes Cells. 2015 Dec; 20 (12): 1006–16.

Germain E, Roghanian M, Gerdes K, Maisonneuve E. Stochastic induction of persister cells by HipA through (p)ppGpp-mediated activation of mRNA endonucleases. Proc Natl Acad Sci U S A. 2015 Apr 21; 112 (16): 5171–6.

Harms A, Maisonneuve E, Gerdes K. Mechanisms of bacterial persistence during stress and antibiotic exposure. Science. 2016 Dec 16; 354 (6318)

Bernier SP, Lebeaux D, DeFrancesco AS, Valomon A, Soubigou G, Coppée J-Y, et al. Starvation, together with the SOS response, mediates high biofilm-specific tolerance to the fluoroquinolone ofloxacin. PLoS Genet. 2013; 9 (1): e 1003144

Nguyen D, Joshi-Datar A, Lepine F, Bauerle E, Olakanmi O, Beer K, et al. Active starvation responses mediate antibiotic tolerance in biofilms and nutrient-limited bacteria. Science. Nov 18; 334 (6058): 982-6.

Wu J, Xie J. Magic spot: (p) ppGpp. J Cell Physiol. 2009 Aug; 220 (2): 297–302.

Van Delden C, Comte R, Bally AM. Stringent response activates quorum sensing and modulates cell density-dependent gene expression in Pseudomonas aeruginosa. J Bacteriol. 2001 Sep; 183 (18): 5376–84.

Lewis K. Persister Cells and the Paradox of Chronic Infections. Microbe Mag. 2010 Oct; 5 (10): 429–37.

Jayaraman R. Bacterial persistence: some new insights into an old phenomenon. J Biosci. 2008 Dec; 33 (5): 795–805.

Rhen M, Eriksson S, Clements M, Bergström S, Normark SJ. The basis of persistent bacterial infections. Trends Microbiol. 2003 Feb; 11 (2): 80–6.

Casellas JM. Resistencia a los antibacterianos en América Latina: consecuencias para la infectología. Rev Panam Salud Pública. 2011;30 (6): 519–28.

Wood TK. Strategies for combating persister cell and biofilm infections. Microb Biotechnol. 2017 Sep;10 (5): 1054–6.

Flemming HC, Wingender J. The biofilm matrix. Nat Rev Microbiol. 2010 Sep; 8 (9): 623–33.

Henry TC, Brynildsen MP. Development of Persister-FACSeq: a method to massively parallelize quantification of persister physiology and its heterogeneity. Sci Rep. 2016 May 4; 6: 25100.

Donlan RM. Role of biofilms in antimicrobial resistance. Asaio J. 2000 Nov-Dec; 46 (6): S 47–52.

Moker N, Dean CR, Tao J. Pseudomonas aeruginosa increases formation of multidrug-tolerant persister cells in response to quorum-sensing signaling molecules. J Bacteriol. 2010 Apr 1; 192 (7):1946–55.

LaFleur MD, Qi Q, Lewis K. Patients with long-term oral carriage harbor high-persister mutants of Candida albicans. Antimicrob Agents Chemother. 2010 Jan;54 (1): 39–44.

Bahar AA, Liu Z, Totsingan F, Buitrago C, Kallenbach N, Ren D. Synthetic dendrimeric peptide active against biofilm and persister cells of Pseudomonas aeruginosa. Appl Microbiol Biotechnol. 2015 Oct; 99 (19): 8125–35.

Wang F, Sambandan D, Halder R, Wang J, Batt SM, Weinrick B, et al. Identification of a small molecule with activity against drug-resistant and persistent tuberculosis. Proc Natl Acad Sci U S A. 2013 Jul 2; 110 (27): E2510-7

Shi W, Zhang X, Jiang X, Yuan H, Lee JS, Barry CE, et al. Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis. Science. 2011 Sep 16; 333 (6049): 1630-2.

Zhang Y, Mitchison D. The curious characteristics of pyrazinamide: a review. Int J Tuberc Lung Dis. 2003 Jan; 7 (1): 6–21.

Deye GA, Gettayacamin M, Hansukjariya P, Im-erbsin R, Sattabongkot J, Rothstein Y, et al. Use of a rhesus Plasmodium cynomolgi model to screen for anti-hypnozoite activity of pharmaceutical substances. Am J Trop Med Hyg. 2012 Jun; 86 (6): 931–5.

Feng J, Weitner M, Shi W, Zhang S, Zhang Y. Eradication of Biofilm-Like Microcolony Structures of Borrelia burgdorferi by Daunomycin and Daptomycin but not Mitomycin C in Combination with Doxycycline and Cefuroxime. Front Microbiol. 2016 Feb 10; 7:62.

Knudsen GM, Ng Y, Gram L. Survival of bactericidal antibiotic treatment by a persister subpopulation of Listeria monocytogenes. Appl Environ Microbiol. 2013 Dec; 79 (23): 7390–7.

Kim S, Lieberman TD, Kishony R. Alternating antibiotic treatments constrain evolutionary paths to multidrug resistance. Proc Natl Acad Sci U S A. 2014 Oct 7; 111 (40): 14494–9.

Allison KR, Brynildsen MP, Collins JJ. Metabolite-enabled eradication of bacterial persisters by aminoglycosides. Nature. 2011 May 12; 473 (7346): 216–20.

Orman MA, Brynildsen MP. Establishment of a method to rapidly assay bacterial persister metabolism. Antimicrob Agents Chemother. 2013 Sep; 57 (9): 4398–409.

Marques CNH, Morozov A, Planzos P, Zelaya HM. The Fatty Acid Signaling Molecule cis-2-Decenoic Acid Increases Metabolic Activity and Reverts Persister Cells to an Antimicrobial-Susceptible State. Appl Environ Microbiol. 2014 Nov; 80 (22): 6976-91.

Byrne ST, Denkin SM, Zhang Y. Aspirin and ibuprofen enhance pyrazinamide treatment of murine tuberculosis. J Antimicrob Chemother. 2007 Feb; 59 (2): 313–6.

Somoskovi A, Wade MM, Sun Z, Zhang Y. Iron enhances the antituberculous activity of pyrazinamide. J Antimicrob Chemother. 2004 Feb; 53 (2): 192–6.

Morones-Ramirez JR, Winkler JA, Spina CS, Collins JJ. Silver Enhances Antibiotec Activity Against Gram-Negative Bacteria. Sci Transl Med. 2013 Jun 19; 5 (190): 1–11.

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Publicado

2020-03-26

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Suclupe-Campos D-O, Aguilar-Gamboa F-R. Persistencia bacteriana: un fenotipo celular de importancia clínica en infecciones crónicas y recurrentes. Horiz Med [Internet]. 26 de marzo de 2020 [citado 29 de marzo de 2024];20(1):77-8. Disponible en: https://www.horizontemedico.usmp.edu.pe/index.php/horizontemed/article/view/767

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