Increased Capsule Thickness and Hypermotility Are Traits of Carbapenem-Resistant ST3 Strains Causing Fulminant Infection

Overview

Journal Open Forum Infect Dis

Specialty Infectious Diseases

Date 2021 Sep 13

PMID 34514017

Citations 4

Authors

Nadya Rakovitsky

Jonathan Lellouche

Debby Ben David

Sammy Frenk

Polet Elmalih

Gabriel Weber

Hadas Kon

David Schwartz

Liat Wolfhart

Elizabeth Temkin

Yehuda Carmeli

Affiliations

Soon will be listed here.

Abstract

Background: is a successful nosocomial pathogen, causing severe, life-threatening infections in hospitalized patients, including pneumonia and bloodstream infections. The spread of carbapenem-resistant (CRAB) strains is a major health threat worldwide. The successful spread of CRAB is mostly due to its highly plastic genome. Although some virulence factors associated with CRAB have been uncovered, many mechanisms contributing to its success are not fully understood.

Methods: Here we describe strains of CRAB that were isolated from fulminant cases in 2 hospitals in Israel. These isolates show a rare hypermucoid (HM) phenotype and were investigated using phenotypic assays, comparative genomics, and an in vivo model.

Results: The 3 isolates belonged to the ST3 international clonal type and were closely related to each other, as shown by Fourier-transform infrared spectroscopy and phylogenetic analyses. These isolates possessed thickened capsules and a dense filamentous extracellular polysaccharides matrix as shown by transmission electron microscopy (TEM), and overexpressed the capsule polysaccharide synthesis pathway-related gene.

Conclusions: The HM isolates possessed a unique combination of virulence genes involved in iron metabolism, protein secretion, adherence, and membrane glycosylation. HM strains were more virulent than control strains in 2 infection models. In conclusion, our findings demonstrated several virulence factors, all present in 3 CRAB isolates with rare hypermucoid phenotypes.

Citing Articles

Phage-encoded depolymerases as a strategy for combating multidrug-resistant .

Islam M, Mahbub N, Shin W, Oh M Front Cell Infect Microbiol. 2024; 14:1462620.

PMID: 39512587 PMC: 11540826. DOI: 10.3389/fcimb.2024.1462620.

Exploring Roles of the Polysaccharide Capsule in Pathogenesis of Hypervirulent Clinical Isolate Lac-4.

Bjanes E, Koh T, Qayum T, Zurich R, McCabe S, Hampel K Antibiotics (Basel). 2024; 13(1).

PMID: 38275320 PMC: 10812722. DOI: 10.3390/antibiotics13010010.

Phenotypic and Genomic Characterization of Nine String-Positive Carbapenem-Resistant Acinetobacter baumannii Isolates from Israel.

Rakovitsky N, Lurie-Weinberger M, Hameir A, Wulffhart L, Keren Paz A, Schwartz D Microbiol Spectr. 2023; :e0300222.

PMID: 36719216 PMC: 10100839. DOI: 10.1128/spectrum.03002-22.

The Wzi outer membrane protein mediates assembly of a tight capsular polysaccharide layer on the Acinetobacter baumannii cell surface.

Tickner J, Hawas S, Totsika M, Kenyon J Sci Rep. 2021; 11(1):21741.

PMID: 34741090 PMC: 8571296. DOI: 10.1038/s41598-021-01206-5.

References

Abdollahi S, Rasooli I, Mousavi Gargari S . The role of TonB-dependent copper receptor in virulence of Acinetobacter baumannii. Infect Genet Evol. 2018; 60:181-190. DOI: 10.1016/j.meegid.2018.03.001. View

Bassetti M, Echols R, Matsunaga Y, Ariyasu M, Doi Y, Ferrer R . Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): a randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3.... Lancet Infect Dis. 2020; 21(2):226-240. DOI: 10.1016/S1473-3099(20)30796-9. View

Hua X, Zhou Z, Yang Q, Shi Q, Xu Q, Wang J . Evolution of : International Clone II, More Resistance to Ceftazidime, Mutation in . Front Microbiol. 2017; 8:1256. PMC: 5502287. DOI: 10.3389/fmicb.2017.01256. View

Pan Y, Lin T, Chen C, Chen Y, Hsieh P, Hsu C . Genetic analysis of capsular polysaccharide synthesis gene clusters in 79 capsular types of Klebsiella spp. Sci Rep. 2015; 5:15573. PMC: 4616057. DOI: 10.1038/srep15573. View

Peleg A, Jara S, Monga D, Eliopoulos G, Moellering Jr R, Mylonakis E . Galleria mellonella as a model system to study Acinetobacter baumannii pathogenesis and therapeutics. Antimicrob Agents Chemother. 2009; 53(6):2605-9. PMC: 2687231. DOI: 10.1128/AAC.01533-08. View

Kenyon J, Hall R . Variation in the complex carbohydrate biosynthesis loci of Acinetobacter baumannii genomes. PLoS One. 2013; 8(4):e62160. PMC: 3628348. DOI: 10.1371/journal.pone.0062160. View

Gu D, Dong N, Zheng Z, Lin D, Huang M, Wang L . A fatal outbreak of ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae in a Chinese hospital: a molecular epidemiological study. Lancet Infect Dis. 2017; 18(1):37-46. DOI: 10.1016/S1473-3099(17)30489-9. View

Dickstein Y, Leibovici L, Yahav D, Eliakim-Raz N, Daikos G, Skiada A . Multicentre open-label randomised controlled trial to compare colistin alone with colistin plus meropenem for the treatment of severe infections caused by carbapenem-resistant Gram-negative infections (AIDA): a study protocol. BMJ Open. 2016; 6(4):e009956. PMC: 4838684. DOI: 10.1136/bmjopen-2015-009956. View

McQueary C, Kirkup B, Si Y, Barlow M, Actis L, Craft D . Extracellular stress and lipopolysaccharide modulate Acinetobacter baumannii surface-associated motility. J Microbiol. 2012; 50(3):434-43. DOI: 10.1007/s12275-012-1555-1. View

10.

Hua M, Liu J, Du P, Liu X, Li M, Wang H . The novel outer membrane protein from OprD/Occ family is associated with hypervirulence of carbapenem resistant Acinetobacter baumannii ST2/KL22. Virulence. 2020; 12(1):1-11. PMC: 7781578. DOI: 10.1080/21505594.2020.1856560. View

11.

Karah N, Dwibedi C, Sjostrom K, Edquist P, Johansson A, Nyunt Wai S . Novel Aminoglycoside Resistance Transposons and Transposon-Derived Circular Forms Detected in Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates. Antimicrob Agents Chemother. 2016; 60(3):1801-18. PMC: 4776018. DOI: 10.1128/AAC.02143-15. View

12.

Hamidian M, Hall R . Genetic structure of four plasmids found in Acinetobacter baumannii isolate D36 belonging to lineage 2 of global clone 1. PLoS One. 2018; 13(9):e0204357. PMC: 6160057. DOI: 10.1371/journal.pone.0204357. View

13.

de Breij A, Eveillard M, Dijkshoorn L, van den Broek P, Nibbering P, Joly-Guillou M . Differences in Acinetobacter baumannii strains and host innate immune response determine morbidity and mortality in experimental pneumonia. PLoS One. 2012; 7(2):e30673. PMC: 3275605. DOI: 10.1371/journal.pone.0030673. View

14.

Kenyon J, Marzaioli A, Hall R, De Castro C . Structure of the K2 capsule associated with the KL2 gene cluster of Acinetobacter baumannii. Glycobiology. 2014; 24(6):554-63. DOI: 10.1093/glycob/cwu024. View

15.

Clemmer K, Bonomo R, Rather P . Genetic analysis of surface motility in Acinetobacter baumannii. Microbiology (Reading). 2011; 157(Pt 9):2534-2544. PMC: 3352170. DOI: 10.1099/mic.0.049791-0. View

16.

Tipton K, Dimitrova D, Rather P . Phase-Variable Control of Multiple Phenotypes in Acinetobacter baumannii Strain AB5075. J Bacteriol. 2015; 197(15):2593-9. PMC: 4518826. DOI: 10.1128/JB.00188-15. View

17.

Lee H, Baek J, Kim S, Jo H, Kang K, Ko J . Comparison of virulence between matt and mucoid colonies of Klebsiella pneumoniae coproducing NDM-1 and OXA-232 isolated from a single patient. J Microbiol. 2018; 56(9):665-672. DOI: 10.1007/s12275-018-8130-3. View

18.

Silva I, Tavares A, Ferreira A, Moreira L . Stress conditions triggering mucoid morphotype variation in Burkholderia species and effect on virulence in Galleria mellonella and biofilm formation in vitro. PLoS One. 2013; 8(12):e82522. PMC: 3865030. DOI: 10.1371/journal.pone.0082522. View

19.

Nutman A, Lellouche J, Lifshitz Z, Glick R, Carmeli Y . In vivo Fitness of Strains in Murine Infection Is Associated with International Lineage II-rep-2 and International Lineage III Clones Showing High Case Fatality Rates in Human Infections. Microorganisms. 2020; 8(6). PMC: 7356693. DOI: 10.3390/microorganisms8060847. View

20.

Chin C, Tipton K, Farokhyfar M, Burd E, Weiss D, Rather P . A high-frequency phenotypic switch links bacterial virulence and environmental survival in Acinetobacter baumannii. Nat Microbiol. 2018; 3(5):563-569. PMC: 5921939. DOI: 10.1038/s41564-018-0151-5. View