umu.sePublications
Change search
Link to record
Permanent link

Direct link
BETA
Ahmad, Irfan
Publications (4 of 4) Show all publications
Ahmad, I., Karah, N., Nadeem, A., Wai, S. N. & Uhlin, B. E. (2019). Analysis of colony phase variation switch in Acinetobacter baumannii clinical isolates. PLoS ONE, 14(1), Article ID e0210082.
Open this publication in new window or tab >>Analysis of colony phase variation switch in Acinetobacter baumannii clinical isolates
Show others...
2019 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 1, article id e0210082Article in journal (Refereed) Published
Abstract [en]

Reversible switching between opaque and translucent colony formation is a novel feature of Acinetobacter baumannii that has been associated with variations in the cell morphology, surface motility, biofilm formation, antibiotic resistance and virulence. Here, we assessed a number of phenotypic alterations related to colony switching in A. baumannii clinical isolates belonging to different multi-locus sequence types. Our findings demonstrated that these phenotypic alterations were mostly strain-specific. In general, the translucent subpopulations of A. baumannii produced more dense biofilms, were more piliated, and released larger amounts of outer membrane vesicles (OMVs). In addition, the translucent subpopulations caused reduced fertility of Caenorhabditis elegans. When assessed for effects on the immune response in RAW 264.7 macrophages, the OMVs isolated from opaque subpopulations of A. baumannii appeared to be more immunogenic than the OMVs from the translucent form. However, also the OMVs from the translucent subpopulations had the potential to evoke an immune response. Therefore, we suggest that OMVs may be considered for development of new immunotherapeutic treatments against A. baumannii infections.

Place, publisher, year, edition, pages
Public Library Science, 2019
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-155634 (URN)10.1371/journal.pone.0210082 (DOI)000454952800043 ()30608966 (PubMedID)
Funder
Swedish Research Council, 2015-03007Swedish Research Council, 2015-06824Swedish Research Council, 2016-06598Swedish Research Council, 349-2007-8673Swedish Research Council, 829-2006-7431The Kempe Foundations, JCK-1527The Kempe Foundations, JCK-1724
Available from: 2019-01-25 Created: 2019-01-25 Last updated: 2019-01-25Bibliographically approved
Ahmad, I., Cimdins, A., Beske, T. & Römling, U. (2017). Detailed analysis of c-di-GMP mediated regulation of csgD expression in Salmonella typhimurium. BMC Microbiology, 17, Article ID 27.
Open this publication in new window or tab >>Detailed analysis of c-di-GMP mediated regulation of csgD expression in Salmonella typhimurium
2017 (English)In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 17, article id 27Article in journal (Refereed) Published
Abstract [en]

Background: The secondary messenger cyclic di-GMP promotes biofilm formation by up regulating the expression of csgD, encoding the major regulator of rdar biofilm formation in Salmonella typhimurium. The GGDEF/EAL domain proteins regulate the c-di-GMP turnover. There are twenty-two GGDEF/EAL domain proteins in the genome of S. typhimurium. In this study, we dissect the role of individual GGDEF/EAL proteins for csgD expression and rdar biofilm development. Results: Among twelve GGDEF domains, two proteins upregulate and among fifteen EAL domains, four proteins down regulate csgD expression. We identified two additional GGDEF proteins required to promote optimal csgD expression. With the exception of the EAL domain of STM1703, solely, diguanylate cyclase and phosphodiesterase activities are required to regulate csgD mediated rdar biofilm formation. Identification of corresponding phosphodiesterases and diguanylate cyclases interacting in the csgD regulatory network indicates various levels of regulation by c-di-GMP. The phosphodiesterase STM1703 represses transcription of csgD via a distinct promoter upstream region. Conclusion: The enzymatic activity and the protein scaffold of GGDEF/EAL domain proteins regulate csgD expression. Thereby, c-di-GMP adjusts csgD expression at multiple levels presumably using a multitude of input signals.

Keywords
c-di-GMP, CsgD, GGDEF/EAL domain proteins, rdar morphotype, biofilm formation, Salmonella typhimurium
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-132130 (URN)10.1186/s12866-017-0934-5 (DOI)000393328800001 ()28148244 (PubMedID)
Available from: 2017-03-09 Created: 2017-03-09 Last updated: 2018-06-09Bibliographically approved
El Mouali, Y., Kim, H., Ahmad, I., Brauner, A., Liu, Y., Skurnik, M., . . . Romling, U. (2017). Stand-Alone EAL Domain Proteins Form a Distinct Subclass of EAL Proteins Involved in Regulation of Cell Motility and Biofilm Formation in Enterobacteria. Journal of Bacteriology, 199(18), Article ID e00179-17.
Open this publication in new window or tab >>Stand-Alone EAL Domain Proteins Form a Distinct Subclass of EAL Proteins Involved in Regulation of Cell Motility and Biofilm Formation in Enterobacteria
Show others...
2017 (English)In: Journal of Bacteriology, ISSN 0021-9193, E-ISSN 1098-5530, Vol. 199, no 18, article id e00179-17Article in journal (Refereed) Published
Abstract [en]

The second messenger cyclic dimeric GMP (c-di-GMP) is almost ubiquitous among bacteria as are the c-di-GMP turnover proteins, which mediate the transition between motility and sessility. EAL domain proteins have been characterized as c-di-GMP-specific phosphodiesterases. While most EAL domain proteins contain additional, usually N-terminal, domains, there is a distinct family of proteins with stand-alone EAL domains, exemplified by Salmonella enterica serovar Typhimurium proteins STM3611 (YhjH/PdeH), a c-di-GMP-specific phosphodiesterase, and the enzymatically inactive STM1344 (YdiV/CdgR) and STM1697, which regulate bacterial motility through interaction with the flagellar master regulator, FlhDC. We have analyzed the phylogenetic distribution of EAL-only proteins and their potential functions. Genes encoding EAL-only proteins were found in various bacterial phyla, although most of them were seen in proteobacteria, particularly enterobacteria. Based on the conservation of the active site residues, nearly all stand-alone EAL domains encoded by genomes from phyla other than proteobacteria appear to represent functional phosphodiesterases. Within enterobacteria, EAL-only proteins were found to cluster either with YhjH or with one of the subfamilies of YdiV-related proteins. EAL-only proteins from Shigella flexneri, Klebsiella pneumoniae, and Yersinia enterocolitica were tested for their ability to regulate swimming and swarming motility and formation of the red, dry, and rough (rdar) biofilm morphotype. In these tests, YhjH-related proteins S4210, KPN_01159, KPN_03274, and YE4063 displayed properties typical of enzymatically active phosphodiesterases, whereas S1641 and YE1324 behaved like members of the YdiV/STM1697 subfamily, with Yersinia enterocolitica protein YE1324 shown to downregulate motility in its native host. Of two closely related EAL-only proteins, YE2225 is an active phosphodiesterase, while YE1324 appears to interact with FlhD. These results suggest that in FlhDC-harboring beta-and gammaproteobacteria, some EAL-only proteins evolved to become catalytically inactive and regulate motility and biofilm formation by interacting with FlhDC. IMPORTANCE The EAL domain superfamily consists mainly of proteins with cyclic dimeric GMP-specific phosphodiesterase activity, but individual domains have been classified in three classes according to their functions and conserved amino acid signatures. Proteins that consist solely of stand-alone EAL domains cannot rely on other domains to form catalytically active dimers, and most of them fall into one of two distinct classes: catalytically active phosphodiesterases with well-conserved residues of the active site and the dimerization loop, and catalytically inactive YdiV/CdgR-like proteins that regulate bacterial motility by binding to the flagellar master regulator, FlhDC, and are found primarily in enterobacteria. The presence of apparently inactive EAL-only proteins in the bacteria that do not express FlhD suggests the existence of additional EAL interaction partners.

Place, publisher, year, edition, pages
American Society for Microbiology, 2017
Keywords
cyclic di-GMP phosphodiesterase, flagellar regulon, motility, protein-protein interaction, FlhDC
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-139132 (URN)10.1128/JB.00179-17 (DOI)000408202300011 ()
Available from: 2017-10-03 Created: 2017-10-03 Last updated: 2018-06-09Bibliographically approved
Ahmad, I., Rouf, S. F., Sun, L., Cimdins, A., Shafeeq, S., Le Guyon, S., . . . Romling, U. (2016). BcsZ inhibits biofilm phenotypes and promotes virulence by blocking cellulose production in Salmonella enterica serovar Typhimurium. Microbial Cell Factories, 15, Article ID 177.
Open this publication in new window or tab >>BcsZ inhibits biofilm phenotypes and promotes virulence by blocking cellulose production in Salmonella enterica serovar Typhimurium
Show others...
2016 (English)In: Microbial Cell Factories, ISSN 1475-2859, E-ISSN 1475-2859, Vol. 15, article id 177Article in journal (Refereed) Published
Abstract [en]

Background: Cellulose, a 1,4 beta-glucan polysaccharide, is produced by a variety of organisms including bacteria. Although the production of cellulose has a high biological, ecological and economical impact, regulatory mechanisms of cellulose biosynthesis are mostly unknown. Family eight cellulases are regularly associated with cellulose biosynthesis operons in bacteria; however, their function is poorly characterized. In this study, we analysed the role of the cellulase BcsZ encoded by the bcsABZC cellulose biosynthesis operon of Salmonella enterica serovar Typhimurium (S. Typhimurium) in biofilm related behavior. We also investigated the involvement of BcsZ in pathogenesis of S. Typhimurium including a murine typhoid fever infection model. Result: In S. Typhimurium, cellulase BcsZ with a putative periplasmic location negatively regulates cellulose biosynthesis. Moreover, as assessed with a non-polar mutant, BcsZ affects cellulose-associated phenotypes such as the rdar biofilm morphotype, cell clumping, biofilm formation, pellicle formation and flagella-dependent motility. Strikingly, although upregulation of cellulose biosynthesis was not observed on agar plate medium at 37 degrees C, BcsZ is required for efficient pathogen-host interaction. Key virulence phenotypes of S. Typhimurium such as invasion of epithelial cells and proliferation in macrophages were positively regulated by BcsZ. Further on, a bcsZ mutant was outcompeted by the wild type in organ colonization in the murine typhoid fever infection model. Selected phenotypes were relieved upon deletion of the cellulose synthase BcsA and/or the central biofilm activator CsgD. Conclusion: Although the protein scaffold has an additional physiological role, our findings indicate that the catalytic activity of BcsZ effectively downregulates CsgD activated cellulose biosynthesis. Repression of cellulose production by BcsZ subsequently enables Salmonella to efficiently colonize the host.

Keywords
Cellulose, Cellulase, BcsZ, Biofilm, CsgD, Salmonella
National Category
Microbiology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-127601 (URN)10.1186/s12934-016-0576-6 (DOI)000385728300001 ()27756305 (PubMedID)
Available from: 2016-12-07 Created: 2016-11-16 Last updated: 2018-06-09Bibliographically approved

Search in DiVA

Show all publications