A Burkholderia Cepacia Complex Non-ribosomal Peptide-synthesized Toxin is Hemolytic and Required for Full Virulence

Overview

Journal Virulence

Specialty Microbiology

Date 2012 May 2

PMID 22546908

Citations 16

Authors

Euan L S Thomson

Jonathan J Dennis

Affiliations

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Abstract

Members of the Burkholderia cepacia complex (Bcc) have recently gained notoriety as significant bacterial pathogens due to their extreme levels of antibiotic resistance, their transmissibility in clinics, their persistence in bacteriostatic solutions, and their intracellular survival capabilities. As pathogens, the Bcc are known to elaborate a number of virulence factors including proteases, lipases and other exoproducts, as well as a number of secretion system associated effectors. Through random and directed mutagenesis studies, we have identified a Bcc gene cluster capable of expressing a toxin that is both hemolytic and required for full Bcc virulence. The Bcc toxin is synthesized via a non-ribosomal peptide synthetase mechanism, and appears to be related to the previously identified antifungal compound burkholdine or occidiofungin. Further testing shows mutations to this gene cluster cause a significant reduction in both hemolysis and Galleria mellonella mortality. Mutation to a glycosyltransferase gene putatively responsible for a structural-functional toxin variant causes only partial reduction in hemolysis. Molecular screening identifies the Bcc species containing this gene cluster, of which several strains produce hemolytic activity.

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References

Vasil M, Krieg D, Kuhns J, Ogle J, Shortridge V, Ostroff R . Molecular analysis of hemolytic and phospholipase C activities of Pseudomonas cepacia. Infect Immun. 1990; 58(12):4020-9. PMC: 313771. DOI: 10.1128/iai.58.12.4020-4029.1990. View

Burns J, Wadsworth C, Barry J, Goodall C . Nucleotide sequence analysis of a gene from Burkholderia (Pseudomonas) cepacia encoding an outer membrane lipoprotein involved in multiple antibiotic resistance. Antimicrob Agents Chemother. 1996; 40(2):307-13. PMC: 163107. DOI: 10.1128/AAC.40.2.307. View

Tawfik K, Jeffs P, Bray B, Dubay G, Falkinham J, Mesbah M . Burkholdines 1097 and 1229, potent antifungal peptides from Burkholderia ambifaria 2.2N. Org Lett. 2010; 12(4):664-6. DOI: 10.1021/ol9029269. View

Rose H, Baldwin A, Dowson C, Mahenthiralingam E . Biocide susceptibility of the Burkholderia cepacia complex. J Antimicrob Chemother. 2009; 63(3):502-10. PMC: 2640157. DOI: 10.1093/jac/dkn540. View

Meyers E, Bisacchi G, Dean L, Liu W, Minassian B, Slusarchyk D . Xylocandin: a new complex of antifungal peptides. I. Taxonomy, isolation and biological activity. J Antibiot (Tokyo). 1987; 40(11):1515-9. DOI: 10.7164/antibiotics.40.1515. View

Shoji J, Hinoo H, Kato T, Hattori T, Hirooka K, Tawara K . Isolation of cepafungins I, II and III from Pseudomonas species. J Antibiot (Tokyo). 1990; 43(7):783-7. DOI: 10.7164/antibiotics.43.783. View

Cardona S, Valvano M . An expression vector containing a rhamnose-inducible promoter provides tightly regulated gene expression in Burkholderia cenocepacia. Plasmid. 2005; 54(3):219-28. DOI: 10.1016/j.plasmid.2005.03.004. View

LiPuma J, Spilker T, Gill L, Campbell 3rd P, Liu L, Mahenthiralingam E . Disproportionate distribution of Burkholderia cepacia complex species and transmissibility markers in cystic fibrosis. Am J Respir Crit Care Med. 2001; 164(1):92-6. DOI: 10.1164/ajrccm.164.1.2011153. View

Lim Y, Suh J, Kim S, Hyun B, Kim C, Lee C . Cepacidine A, a novel antifungal antibiotic produced by Pseudomonas cepacia. II. Physico-chemical properties and structure elucidation. J Antibiot (Tokyo). 1994; 47(12):1406-16. DOI: 10.7164/antibiotics.47.1406. View

10.

LiPuma J, Dasen S, Nielson D, Stern R, Stull T . Person-to-person transmission of Pseudomonas cepacia between patients with cystic fibrosis. Lancet. 1990; 336(8723):1094-6. DOI: 10.1016/0140-6736(90)92571-x. View

11.

Gu G, Smith L, Wang N, Wang H, Lu S . Biosynthesis of an antifungal oligopeptide in Burkholderia contaminans strain MS14. Biochem Biophys Res Commun. 2009; 380(2):328-32. DOI: 10.1016/j.bbrc.2009.01.073. View

12.

Jacobsen C, Pedersen J . Mineralization of 2,4-dichlorophenoxyacetic acid (2,4-D) in soil inoculated with Pseudomonas cepacia DBO1(pRO101), Alcaligenes eutrophus AEO106(pRO101) and Alcaligenes eutrophus JMP134(pJP4): effects of inoculation level and substrate concentration. Biodegradation. 1991; 2(4):253-63. DOI: 10.1007/BF00114557. View

13.

Hammer P, BURD W, Hill D, Ligon J, van Pee K . Conservation of the pyrrolnitrin biosynthetic gene cluster among six pyrrolnitrin-producing strains. FEMS Microbiol Lett. 1999; 180(1):39-44. DOI: 10.1111/j.1574-6968.1999.tb08775.x. View

14.

Romero-Gomez M, Quiles-Melero M, Pena Garcia P, Gutierrez Altes A, Garcia de Miguel M, Jimenez C . Outbreak of Burkholderia cepacia bacteremia caused by contaminated chlorhexidine in a hemodialysis unit. Infect Control Hosp Epidemiol. 2008; 29(4):377-8. DOI: 10.1086/529032. View

15.

Buroni S, Pasca M, Flannagan R, Bazzini S, Milano A, Bertani I . Assessment of three Resistance-Nodulation-Cell Division drug efflux transporters of Burkholderia cenocepacia in intrinsic antibiotic resistance. BMC Microbiol. 2009; 9:200. PMC: 2753365. DOI: 10.1186/1471-2180-9-200. View

16.

Walsh T, Ballou D . Halogenated protocatechuates as substrates for protocatechuate dioxygenase from Pseudomonas cepacia. J Biol Chem. 1983; 258(23):14413-21. View

17.

Estivariz C, Bhatti L, Pati R, Jensen B, Arduino M, Jernigan D . An outbreak of Burkholderia cepacia associated with contamination of albuterol and nasal spray. Chest. 2006; 130(5):1346-53. DOI: 10.1378/chest.130.5.1346. View

18.

Fehlner-Gardiner C, Valvano M . Identification of a general secretory pathway in a human isolate of Burkholderia vietnamiensis (formerly B. cepacia complex genomovar V) that is required for the secretion of hemolysin and phospholipase C activities. Microb Pathog. 2002; 32(5):249-54. DOI: 10.1006/mpat.2002.0503. View

19.

Nakazawa T, Yamada Y, Ishibashi M . Characterization of hemolysin in extracellular products of Pseudomonas cepacia. J Clin Microbiol. 1987; 25(2):195-8. PMC: 265865. DOI: 10.1128/jcm.25.2.195-198.1987. View

20.

Winkelmann G . Pyrrolnitrin from Burkholderia cepacia: antibiotic activity against fungi and novel activities against streptomycetes. J Appl Microbiol. 1998; 85(1):69-78. DOI: 10.1046/j.1365-2672.1998.00473.x. View