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Publications (10 of 14) Show all publications
Mushtaq, F., Nadeem, A., Yabrag, A., Bala, A., Karah, N., Zlatkov, N., . . . Ahmad, I. (2024). Colony phase variation switch modulates antimicrobial tolerance and biofilm formation in Acinetobacter baumannii. Microbiology Spectrum, 12(2), Article ID e02956-23.
Open this publication in new window or tab >>Colony phase variation switch modulates antimicrobial tolerance and biofilm formation in Acinetobacter baumannii
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2024 (English)In: Microbiology Spectrum, E-ISSN 2165-0497, Vol. 12, no 2, article id e02956-23Article in journal (Refereed) Published
Abstract [en]

Carbapenem-resistant Acinetobacter baumannii causes one of the most difficult-to-treat nosocomial infections. Polycationic drugs like polymyxin B or colistin and tetracycline drugs such as doxycycline or minocycline are commonly used to treat infections caused by carbapenem-resistant A. baumannii. Here, we show that a subpopulation of cells associated with the opaque/translucent colony phase variation by A. baumannii AB5075 displays differential tolerance to subinhibitory concentrations of colistin and tetracycline. Using a variety of microscopic techniques, we demonstrate that extracellular polysaccharide moieties mediate colistin tolerance to opaque A. baumannii at single-cell level and that mushroom-shaped biofilm structures protect opaque bacteria at the community level. The colony switch phenotype is found to alter several traits of A. baumannii, including long-term survival under desiccation, tolerance to ethanol, competition with Escherichia coli, and intracellular survival in the environmental model host Acanthamoeba castellanii. Additionally, our findings suggest that extracellular DNA associated with membrane vesicles can promote colony switching in a DNA recombinase-dependent manner.

Importance: As a WHO top-priority drug-resistant microbe, Acinetobacter baumannii significantly contributes to hospital-associated infections worldwide. One particularly intriguing aspect is its ability to reversibly switch its colony morphotype on agar plates, which has been remarkably underexplored. In this study, we employed various microscopic techniques and phenotypic assays to investigate the colony phase variation switch under different clinically and environmentally relevant conditions. Our findings reveal that the presence of a poly N-acetylglucosamine-positive extracellular matrix layer contributes to the protection of bacteria from the bactericidal effects of colistin. Furthermore, we provide intriguing insights into the multicellular lifestyle of A. baumannii, specifically in the context of colony switch variation within its predatory host, Acanthamoeba castellanii.

Place, publisher, year, edition, pages
American Society for Microbiology, 2024
Keywords
colisitin, opaque colony, translucent colony
National Category
Infectious Medicine Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-221121 (URN)10.1128/spectrum.02956-23 (DOI)001141161500001 ()38205963 (PubMedID)2-s2.0-85184519514 (Scopus ID)
Funder
Swedish Research Council, 2020-06136Swedish Research Council, 2019-01720Swedish Research Council, 2018-02914Swedish Research Council, 2016-00968Swedish Research Council, 2019-00217The Kempe Foundations, SMK-1961The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), IB2022-9222Swedish Cancer Society, 2017-419
Available from: 2024-02-20 Created: 2024-02-20 Last updated: 2024-02-20Bibliographically approved
Zlatkov, N., Gunnari, W. & Resch, U. (2024). Comparative label-free proteomics of the neonatal meningitis-causing Escherichia coli K1 IHE3034 and RS218 morphotypes. Microbiology Resource Announcements, 13(2), Article ID e00960-23.
Open this publication in new window or tab >>Comparative label-free proteomics of the neonatal meningitis-causing Escherichia coli K1 IHE3034 and RS218 morphotypes
2024 (English)In: Microbiology Resource Announcements, E-ISSN 2576-098X, Vol. 13, no 2, article id e00960-23Article in journal (Refereed) Published
Abstract [en]

The proteome of two newborn meningitis Escherichia coli K1 (NMEC) morphotypes was examined via a label-free proteomics approach. Besides shared NMEC virulence factors, the two strains have different evolutionary strategies-strain IHE3034 tends to perform anaerobic respiration continuously, while strain RS218 maintains its filamentous morphotype due to active SOS response.

Place, publisher, year, edition, pages
American Society for Microbiology, 2024
Keywords
ExPEC, newborn meningitis, NMEC, proteomics
National Category
Microbiology Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-222287 (URN)10.1128/mra.00960-23 (DOI)001153943500006 ()38289054 (PubMedID)2-s2.0-85186460566 (Scopus ID)
Funder
Swedish Research Council, 2019-01720The Kempe Foundations, SMK-1961
Available from: 2024-03-25 Created: 2024-03-25 Last updated: 2024-03-25Bibliographically approved
Ahmad, I., Nadeem, A., Mushtaq, F., Zlatkov, N., Shahzad, M., Zavialov, A. V., . . . Uhlin, B. E. (2023). Csu pili dependent biofilm formation and virulence of Acinetobacter baumannii. npj Biofilms and Microbiomes, 9(1), Article ID 101.
Open this publication in new window or tab >>Csu pili dependent biofilm formation and virulence of Acinetobacter baumannii
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2023 (English)In: npj Biofilms and Microbiomes, E-ISSN 2055-5008, Vol. 9, no 1, article id 101Article in journal (Refereed) Published
Abstract [en]

Acinetobacter baumannii has emerged as one of the most common extensive drug-resistant nosocomial bacterial pathogens. Not only can the bacteria survive in hospital settings for long periods, but they are also able to resist adverse conditions. However, underlying regulatory mechanisms that allow A. baumannii to cope with these conditions and mediate its virulence are poorly understood. Here, we show that bi-stable expression of the Csu pili, along with the production of poly-N-acetyl glucosamine, regulates the formation of Mountain-like biofilm-patches on glass surfaces to protect bacteria from the bactericidal effect of colistin. Csu pilus assembly is found to be an essential component of mature biofilms formed on glass surfaces and of pellicles. By using several microscopic techniques, we show that clinical isolates of A. baumannii carrying abundant Csu pili mediate adherence to epithelial cells. In addition, Csu pili suppressed surface-associated motility but enhanced colonization of bacteria into the lungs, spleen, and liver in a mouse model of systemic infection. The screening of c-di-GMP metabolizing protein mutants of A. baumannii 17978 for the capability to adhere to epithelial cells led us to identify GGDEF/EAL protein AIS_2337, here denoted PdeB, as a major regulator of Csu pili-mediated virulence and biofilm formation. Moreover, PdeB was found to be involved in the type IV pili-regulated robustness of surface-associated motility. Our findings suggest that the Csu pilus is not only a functional component of mature A. baumannii biofilms but also a major virulence factor promoting the initiation of disease progression by mediating bacterial adherence to epithelial cells.

Place, publisher, year, edition, pages
Springer Nature, 2023
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-218629 (URN)10.1038/s41522-023-00465-6 (DOI)38097635 (PubMedID)2-s2.0-85179677116 (Scopus ID)
Funder
Swedish Research Council, 2020-06136Swedish Research Council, 2020-06136Swedish Research Council, 2018-02914Swedish Research Council, 2022-04779The Kempe Foundations, SMK-1961The Kempe Foundations, SMK21-0076Umeå University, FS 2.1.6–1776-19Umeå University, 2021-2023The Swedish Foundation for International Cooperation in Research and Higher Education (STINT)Swedish Cancer Society, 2017-419
Available from: 2023-12-27 Created: 2023-12-27 Last updated: 2023-12-27Bibliographically approved
Zlatkov, N., Näsman, M. E. & Uhlin, B. E. (2022). Metabolic and morphotypic trade-offs within the eco-evolutionary dynamics of Escherichia coli. Microbiology Spectrum, 10(5)
Open this publication in new window or tab >>Metabolic and morphotypic trade-offs within the eco-evolutionary dynamics of Escherichia coli
2022 (English)In: Microbiology Spectrum, E-ISSN 2165-0497, Vol. 10, no 5Article in journal (Refereed) Published
Abstract [en]

Escherichia coli arbitrarily encompasses facultative anaerobic, rod-shaped bacteria with defined respiratory and fermentative types of metabolism. The species diversification has been further advanced by atypical strains whose features deviate from the essential species-specific morphological and metabolic cutoff. The morphological cutoff is exemplified by bacterial filamentation. E. coli filamentation has been studied from two different perspectives: the first considers filamentation as a result of adaptive strategies and response to stress, while the second is based on findings from the cell division of E. coli’s conditional mutants. Another cutoff is represented by E. coli’s inability to use citrate as a sole carbon and energy source. In this study, we compared two atypical E. coli strains that belong to the same neuroinvasive ecovar but exhibit either of the two phenotypes that deviate from the species’ features. While E. coli RS218 exists in the form of filaments incapable of growth on citrate, strain IHE3034 is represented as normal-sized bacteria able to ferment citrate under oxic conditions in the presence of glucose; in this paper, we show that these two phenotypes result from a bona fide trade-off. With the help of comparative proteomics and metabolomics, we discovered the proteome required for the upkeep of these phenotypes. The metabolic profiles of both strains reveal that under aerobic conditions, RS218 undergoes oxidative metabolism, while IHE3034 undergoes anaerobic respiration. Finally, we show that the use of citrate and filament formation are both linked in a trade-off occurring via a c-di-GMP-dependent phase variation event. IMPORTANCE Aerobic use of citrate and filamentous growth are arbitrary cutoffs for the Escherichia coli species. The strains that exhibit them as stable phenotypes are called atypical. In this study, we compare two atypical neuroinvasive E. coli strains, which alternatively display either of these phenotypes. We present the proteome and metabolome required for the maintenance of filamentous growth and show that anaerobic nitrate respiration is the main requirement for the use of citrate. The fact that the two phenotypes are differentially expressed by each strain prompted us to check if they are part of a trade-off. Indeed, these atypical characters are reversible and result from a c-di-GMP phase variation event. Thus, we revealed hidden links between stable morphological and metabolic phenotypes and provided information about alternative evolutionary pathways for the survival of E. coli strains in various host niches.

Place, publisher, year, edition, pages
American Society for Microbiology, 2022
Keywords
citrate utilization, Escherichia coli, ExPEC, filamentation, metabolomics, NMEC, phase variation, proteomics
National Category
Microbiology
Identifiers
urn:nbn:se:umu:diva-200888 (URN)10.1128/spectrum.00678-22 (DOI)000861853000001 ()36169422 (PubMedID)2-s2.0-85140855969 (Scopus ID)
Funder
Swedish Research Council, 2019-01720The Kempe Foundations, SMK-1961
Available from: 2022-11-10 Created: 2022-11-10 Last updated: 2023-10-06Bibliographically approved
Nadeem, A., Berg, A., Pace, H., Alam, A., Toh, E., Ådén, J., . . . Wai, S. N. (2022). Protein-lipid interaction at low pH induces oligomerization of the MakA cytotoxin from Vibrio cholerae. eLIFE, 11, Article ID e73439.
Open this publication in new window or tab >>Protein-lipid interaction at low pH induces oligomerization of the MakA cytotoxin from Vibrio cholerae
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2022 (English)In: eLIFE, E-ISSN 2050-084X, Vol. 11, article id e73439Article in journal (Refereed) Published
Abstract [en]

The α-pore-forming toxins (α-PFTs) from pathogenic bacteria damage host cell membranes by pore formation. We demonstrate a remarkable, hitherto unknown mechanism by an α-PFT protein from Vibrio cholerae. As part of the MakA/B/E tripartite toxin, MakA is involved in membrane pore formation similar to other α-PFTs. In contrast, MakA in isolation induces tube-like structures in acidic endosomal compartments of epithelial cells in vitro. The present study unravels the dynamics of tubular growth, which occurs in a pH-, lipid-, and concentration-dependent manner. Within acidified organelle lumens or when incubated with cells in acidic media, MakA forms oligomers and remodels membranes into high-curvature tubes leading to loss of membrane integrity. A 3.7 Å cryo-electron microscopy structure of MakA filaments reveals a unique protein-lipid superstructure. MakA forms a pinecone-like spiral with a central cavity and a thin annular lipid bilayer embedded between the MakA transmembrane helices in its active α-PFT conformation. Our study provides insights into a novel tubulation mechanism of an α-PFT protein and a new mode of action by a secreted bacterial toxin.

Place, publisher, year, edition, pages
eLife Sciences Publications, Ltd, 2022
Keywords
Vibrio cholerae, MakA, lipid
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-192300 (URN)10.7554/eLife.73439 (DOI)2-s2.0-85124321786 (Scopus ID)
Funder
Swedish Research Council, 2018–02914Swedish Research Council, 2016–05009Swedish Research Council, 2019–01720Swedish Research Council, 2016–06963Swedish Research Council, 2019–02011Swedish Cancer Society, 2017–419Swedish Cancer Society, 2020–711The Kempe Foundations, JCK-1728The Kempe Foundations, SMK-1756.2The Kempe Foundations, SMK-1553The Kempe Foundations, JCK-1724The Kempe Foundations, SMK-1961Knut and Alice Wallenberg FoundationFamiljen Erling-Perssons Stiftelse
Available from: 2022-02-08 Created: 2022-02-08 Last updated: 2024-01-12Bibliographically approved
Nadeem, A., Nagampalli, R., Toh, E., Alam, A., Myint, S. L., Heidler, T., . . . Persson, K. (2021). A tripartite cytolytic toxin formed by Vibrio cholerae proteins with flagellum-facilitated secretion. Proceedings of the National Academy of Sciences of the United States of America, 118(47), Article ID e2111418118.
Open this publication in new window or tab >>A tripartite cytolytic toxin formed by Vibrio cholerae proteins with flagellum-facilitated secretion
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2021 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 118, no 47, article id e2111418118Article in journal (Refereed) Published
Abstract [en]

Vibrio cholerae, responsible for outbreaks of cholera disease, is a highly motile organism by virtue of a single flagellum. We describe how the flagellum facilitates the secretion of three V. cholerae proteins encoded by a hitherto-unrecognized genomic island. The proteins MakA/B/E can form a tripartite toxin that lyses erythrocytes and is cytotoxic to cultured human cells. A structural basis for the cytolytic activity of the Mak proteins was obtained by X-ray crystallography. Flagellum-facilitated secretion ensuring spatially coordinated delivery of Mak proteins revealed a role for the V. cholerae flagellum considered of particular significance for the bacterial environmental persistence. Our findings will pave the way for the development of diagnostics and therapeutic strategies against pathogenic Vibrionaceae.

National Category
Biochemistry and Molecular Biology
Research subject
Biochemistry
Identifiers
urn:nbn:se:umu:diva-191257 (URN)10.1073/pnas.2111418118 (DOI)000727697700014 ()34799450 (PubMedID)2-s2.0-85121209218 (Scopus ID)
Funder
Swedish Research Council, 2016-05009Swedish Research Council, 2018-02914Swedish Research Council, 2019-01720Swedish Research Council, 2007-08673The Kempe Foundations, SMK-1756.2The Kempe Foundations, SMK-1553The Kempe Foundations, JCK-1728Swedish Cancer Society, 2017-419The Kempe Foundations, SMK-1961Swedish Research Council
Available from: 2022-01-12 Created: 2022-01-12 Last updated: 2023-05-11Bibliographically approved
Zlatkov, N., Nadeem, A., Uhlin, B. E. & Wai, S. N. (2021). Eco-evolutionary feedbacks mediated by bacterial membrane vesicles. FEMS Microbiology Reviews, 45(2), Article ID fuaa047.
Open this publication in new window or tab >>Eco-evolutionary feedbacks mediated by bacterial membrane vesicles
2021 (English)In: FEMS Microbiology Reviews, ISSN 0168-6445, E-ISSN 1574-6976, Vol. 45, no 2, article id fuaa047Article in journal (Refereed) Published
Abstract [en]

Bacterial membrane vesicles (BMVs) are spherical extracellular organelles whose cargo is enclosed by a biological membrane. The cargo can be delivered to distant parts of a given habitat in a protected and concentrated manner. This review presents current knowledge about BMVs in the context of bacterial eco-evolutionary dynamics among different environments and hosts. BMVs may play an important role in establishing and stabilizing bacterial communities in such environments; for example, bacterial populations may benefit from BMVs to delay the negative effect of certain evolutionary trade-offs that can result in deleterious phenotypes. BMVs can also perform ecosystem engineering by serving as detergents, mediators in biochemical cycles, components of different biofilms, substrates for cross-feeding, defense systems against different dangers and enzyme-delivery mechanisms that can change substrate availability. BMVs further contribute to bacteria as mediators in different interactions, with either other bacterial species or their hosts. In short, BMVs extend and deliver phenotypic traits that can have ecological and evolutionary value to both their producers and the ecosystem as a whole.

Place, publisher, year, edition, pages
Oxford University Press, 2021
Keywords
bacterial membrane vesicles, ecology, evolution
National Category
Microbiology
Identifiers
urn:nbn:se:umu:diva-182115 (URN)10.1093/femsre/fuaa047 (DOI)000637053600001 ()2-s2.0-85103227807 (Scopus ID)
Funder
Swedish Research Council, 2015-03007Swedish Research Council, 2015-06824Swedish Research Council, 2016- 06598Swedish Research Council, 2018-02914Swedish Research Council, 2019-01720Swedish Research Council, 349-2007-8673The Kempe Foundations, JCK-1724The Kempe Foundations, JCK-1728Swedish Cancer Society, 2017-419
Available from: 2021-04-09 Created: 2021-04-09 Last updated: 2023-09-05Bibliographically approved
Myint, S. L., Zlatkov, N., Aung, K. M., Toh, E., Sjöström, A. E., Nadeem, A., . . . Wai, S. N. (2021). Ecotin and LamB in Escherichia coli influence the susceptibility to Type VI secretion-mediated interbacterial competition and killing by Vibrio cholerae. Biochimica et Biophysica Acta - General Subjects, 1865(7), Article ID 129912.
Open this publication in new window or tab >>Ecotin and LamB in Escherichia coli influence the susceptibility to Type VI secretion-mediated interbacterial competition and killing by Vibrio cholerae
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2021 (English)In: Biochimica et Biophysica Acta - General Subjects, ISSN 0304-4165, E-ISSN 1872-8006, Vol. 1865, no 7, article id 129912Article in journal (Refereed) Published
Abstract [en]

Background: A prevailing action of the Type VI secretion system (T6SS) in several Gram-negative bacterial species is inter-bacterial competition. In the past several years, many effectors of T6SS were identified in different bacterial species and their involvement in inter-bacterial interactions were described. However, possible defence mechanisms against T6SS attack among prey bacteria were not well clarified yet. Methods: Escherichia coli was assessed for susceptibility to T6SS-mediated killing by Vibrio cholerae. TheT6SS-mediated bacterial killing assays were performed in absence or presence of different protease inhibitors and with different mutant E. coli strains. Expression levels of selected proteins were monitored using SDS-PAGE and immunoblot analyses. Results: The T6SS-mediated killing of E. coli by V. cholerae was partly blocked when the serine protease inhibitor Pefabloc was present. E. coli lacking the periplasmic protease inhibitor Ecotin showed enhanced susceptibility to killing by V. cholerae. Mutations affecting E. coli membrane stability also caused increased susceptibility to killing by V. cholerae. E. coli lacking the maltodextrin porin protein LamB showed reduced susceptibility to killing by V. cholerae whereas E. coli with induced high levels of LamB showed reduced survival in inter-bacterial competition. Conclusions: Our study identified two proteins in E. coli, the intrinsic protease inhibitor Ecotin and the outer membrane porin LamB, that influenced E. coli susceptibility to T6SS-mediated killing by V. cholerae. General significance: We envision that it is feasible to explore these findings to target and modulate their expression to obtain desired changes in inter-bacterial competition in vivo, e.g. in the gastrointestinal microbiome.

Place, publisher, year, edition, pages
Elsevier, 2021
Keywords
Ecotin, Escherichia coli, Interbacterial competition, LamB, T6SS, Vibrio cholerae
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-182908 (URN)10.1016/j.bbagen.2021.129912 (DOI)000652016000005 ()33892013 (PubMedID)2-s2.0-85104614899 (Scopus ID)
Available from: 2021-05-28 Created: 2021-05-28 Last updated: 2023-09-05Bibliographically approved
Zlatkov, N. & Uhlin, B. E. (2020). Unconventional Cyclic di-GMP Signaling in Escherichia coli (1ed.). In: Chou, Shan-Ho; Guiliani, Nicolas; Lee, Vincent T.; Römling, Ute (Ed.), Microbial Cyclic Di-Nucleotide Signaling: (pp. 487-517). Chambridge: Springer International Publishing
Open this publication in new window or tab >>Unconventional Cyclic di-GMP Signaling in Escherichia coli
2020 (English)In: Microbial Cyclic Di-Nucleotide Signaling / [ed] Chou, Shan-Ho; Guiliani, Nicolas; Lee, Vincent T.; Römling, Ute, Chambridge: Springer International Publishing , 2020, 1, p. 487-517Chapter in book (Other academic)
Abstract [en]

The species Escherichia coli represents an unfathomable variety of commensal, pathogenic, and environmental strains. The conventional cyclic di-GMP signaling in E. coli controls sessility-motility changes linked to commensalism and/or pathogenicity. Extraintestinal Pathogenic E. coli (ExPEC) are “commensals” that can cause an array of infections outside the gastrointestinal tract. To accommodate their pathogenic lifestyle with the commensal one, ExPEC biology is shaped not only by the presence of specific virulence genes and pathoadaptive mutations but also by regulatory adaptations. Bioinformatic and genetic studies indicate that the cyclic di-GMP signaling network is included in the adaptation process. For example, some neuroinvasive ExPEC were found to maintain reduced cyclic di-GMP levels due to RpoS deactivation, resulting in loss of appearance of the rugose morphotype. Moreover, ExPEC has a diversified repertoire of cyclic di-GMP degrading enzymes obtained by acquisition of novel genes often associated with fimbrial biogenesis gene clusters (e.g., sfaY/papY/focY) and by modification or deletion of specific core genome genes. For example, the majority of ExPEC contains a shortened allelic variant of the ycgG gene and some ExPEC strains do not even carry the genetic locus. New combinations of regulators offer a new cyclic di-GMP platform for S-fimbrial biogenesis and for new metabolic capabilities leading to citrate utilization and ferric citrate uptake. In this review, we outline the prerequisites for the unconventional signaling network, the rationale behind its existence in ExPEC, and future perspectives in studies of ExPEC.

Place, publisher, year, edition, pages
Chambridge: Springer International Publishing, 2020 Edition: 1
Keywords
ExPEC, NMEC, Pathoadaptation, RpoS, Citrate, Ferric citrate, S-fimbriae
National Category
Microbiology in the medical area
Research subject
Microbiology
Identifiers
urn:nbn:se:umu:diva-169131 (URN)10.1007/978-3-030-33308-9_29 (DOI)2-s2.0-85119027103 (Scopus ID)978-3-030-33307-2 (ISBN)978-3-030-33308-9 (ISBN)
Funder
Swedish Research Council, 2015-03007Swedish Research Council, 2015-06824Swedish Research Council, 2016-06598Swedish Research Council, 349-2007-8673Swedish Research Council, 829-2006-7431
Available from: 2020-03-21 Created: 2020-03-21 Last updated: 2021-11-23Bibliographically approved
Zlatkov, N. & Uhlin, B. E. (2019). Absence of Global Stress Regulation in Escherichia coli Promotes Pathoadaptation and Novel c-di-GMP-dependent Metabolic Capability. Scientific Reports, 9, Article ID 2600.
Open this publication in new window or tab >>Absence of Global Stress Regulation in Escherichia coli Promotes Pathoadaptation and Novel c-di-GMP-dependent Metabolic Capability
2019 (English)In: Scientific Reports, ISSN 2045-2322, Vol. 9, article id 2600Article in journal (Refereed) Published
Abstract [en]

athoadaptive mutations linked to c-di-GMP signalling were investigated in neonatal meningitis-causing Escherichia coli (NMEC). The results indicated that NMEC strains deficient in RpoS (the global stress regulator) maintained remarkably low levels of c-di-GMP, a major bacterial sessility-motility switch. Deletion of ycgG2, shown here to encode a YcgG allozyme with c-di-GMP phosphodiesterase activity, and the restoration of RpoS led to a decrease in S-fimbriae, robustly produced in artificial urine, hinting that the urinary tract could serve as a habitat for NMEC. We showed that NMEC were skilled in aerobic citrate utilization in the presence of glucose, a property that normally does not exist in E. coli. Our data suggest that this metabolic novelty is a property of extraintestinal pathogenic E. coli since we reconstituted this ability in E. coli UTI89 (a cystitis isolate) via deactivation rpoS; additionally, a set of pyelonephritis E. coli isolates were shown here to aerobically use citrate in the presence of glucose. We found that the main reason for this metabolic capability is RpoS inactivation leading to the production of the citrate transporter CitT, exploited by NMEC for ferric citrate uptake dependent on YcgG2 (an allozyme with c-di-GMP phosphodiesterase activity).

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-155827 (URN)10.1038/s41598-019-39580-w (DOI)000459399400069 ()30796316 (PubMedID)2-s2.0-85062007752 (Scopus ID)
Note

Originally included in thesis in manuscript form.

Available from: 2019-01-29 Created: 2019-01-29 Last updated: 2023-03-24Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0003-3318-9084

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