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  1. Article ; Online: Exploring the resistome, virulome, and mobilome of multidrug-resistant Klebsiella pneumoniae isolates: deciphering the molecular basis of carbapenem resistance.

    Rahmat Ullah, Sidra / Irum, Sidra / Mahnoor, Iqra / Ismatullah, Humaira / Mumtaz, Mariam / Andleeb, Saadia / Rahman, Abdur / Jamal, Muhsin

    BMC genomics

    2024  Volume 25, Issue 1, Page(s) 408

    Abstract: Background: Klebsiella pneumoniae, a notorious pathogen for causing nosocomial infections has become a major cause of neonatal septicemia, leading to high morbidity and mortality worldwide. This opportunistic bacterium has become highly resistant to ... ...

    Abstract Background: Klebsiella pneumoniae, a notorious pathogen for causing nosocomial infections has become a major cause of neonatal septicemia, leading to high morbidity and mortality worldwide. This opportunistic bacterium has become highly resistant to antibiotics due to the widespread acquisition of genes encoding a variety of enzymes such as extended-spectrum beta-lactamases (ESBLs) and carbapenemases. We collected Klebsiella pneumoniae isolates from a local tertiary care hospital from February 2019-February 2021. To gain molecular insight into the resistome, virulome, and genetic environment of significant genes of multidrug-resistant K. pneumoniae isolates, we performed the short-read whole-genome sequencing of 10 K. pneumoniae isolates recovered from adult patients, neonates, and hospital tap water samples.
    Results: The draft genomes of the isolates varied in size, ranging from 5.48 to 5.96 Mbp suggesting the genome plasticity of this pathogen. Various genes conferring resistance to different classes of antibiotics e.g., aminoglycosides, quinolones, sulfonamides, tetracycline, and trimethoprim were identified in all sequenced isolates. The highest resistance was observed towards carbapenems, which has been putatively linked to the presence of both class B and class D carbapenemases, bla
    Conclusions: This study provides valuable insight into the presence of multiple mechanisms of carbapenem resistance in K. pneumoniae strains including the acquisition of multiple antibiotic-resistance genes through mobile genetic elements. Identification of rich mobilome yielded insightful information regarding the crucial role of insertion sequences, transposons, and integrons in shaping the genome of bacteria for the transmission of various resistance-associated genes. Multi-drug resistant isolates that had the fewest resistance genes exhibited a significant number of mutations. K. pneumoniae isolate from water source displayed comparable antibiotic resistance determinants to clinical isolates and the highest number of virulence-associated genes suggesting the possible interplay of ARGs amongst bacteria from different sources.
    MeSH term(s) Klebsiella pneumoniae/genetics ; Klebsiella pneumoniae/drug effects ; Klebsiella pneumoniae/isolation & purification ; Drug Resistance, Multiple, Bacterial/genetics ; Carbapenems/pharmacology ; Humans ; Whole Genome Sequencing ; Genome, Bacterial ; beta-Lactamases/genetics ; Anti-Bacterial Agents/pharmacology ; Phylogeny ; Klebsiella Infections/microbiology ; Klebsiella Infections/drug therapy ; Microbial Sensitivity Tests ; Bacterial Proteins
    Chemical Substances Carbapenems ; beta-Lactamases (EC 3.5.2.6) ; Anti-Bacterial Agents ; carbapenemase (EC 3.5.2.6) ; Bacterial Proteins
    Language English
    Publishing date 2024-04-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041499-7
    ISSN 1471-2164 ; 1471-2164
    ISSN (online) 1471-2164
    ISSN 1471-2164
    DOI 10.1186/s12864-024-10139-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: In-Silico Vaccine Design Based on a Novel Vaccine Candidate Against Infections Caused by

    Khalid, Kashaf / Irum, Sidra / Ullah, Sidra Rahmat / Andleeb, Saadia

    International journal of peptide research and therapeutics

    2021  Volume 28, Issue 1, Page(s) 16

    Abstract: Acinetobacter baumannii: Supplementary information: The online version contains supplementary material available at 10.1007/s10989-021-10316-7. ...

    Abstract Acinetobacter baumannii
    Supplementary information: The online version contains supplementary material available at 10.1007/s10989-021-10316-7.
    Language English
    Publishing date 2021-12-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2192632-3
    ISSN 1573-3904 ; 1573-3149
    ISSN (online) 1573-3904
    ISSN 1573-3149
    DOI 10.1007/s10989-021-10316-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Characterization of exclusively non-commensal Neisseria gonorrhoeae pangenome to prioritize globally conserved and thermodynamically stable vaccine candidates using immune-molecular dynamic simulations.

    Mahnoor, Iqra / Shabbir, Hamna / Nawaz, Shabana / Aziz, Kinza / Aziz, Ubair / Khalid, Kashaf / Irum, Sidra / Andleeb, Saadia

    Microbial pathogenesis

    2023  Volume 185, Page(s) 106439

    Abstract: Neisseria gonorrhoeae (Ngo) has emerged as a global threat leading to one of the most common sexually transmitted diseases in the world. It has also become one of the leading antimicrobial resistant organisms, resulting in fewer treatment options and an ... ...

    Abstract Neisseria gonorrhoeae (Ngo) has emerged as a global threat leading to one of the most common sexually transmitted diseases in the world. It has also become one of the leading antimicrobial resistant organisms, resulting in fewer treatment options and an increased morbidity. Therefore, in recent years, there has been an increased focus on the development of new treatments and preventive strategies to combat its infection. In this study, we have combined the most conserved epitopes from the completely assembled strains of Ngo to develop a universal and a thermodynamically stable vaccine candidate. For our vaccine design, the epitopes were selected for their high immunogenicity, non-allergenicity and non-cytotoxicity, making them the ideal candidates for vaccine development. For the screening process, several reverse vaccinology tools were employed to rigorously extract non-homologous and immunogenic epitopes from the selected proteins. Consequently, a total number of 3 B-cell epitopes and 6 T-cell epitopes were selected and joined by multiple immune-modulating adjuvants and linkers to generate a promiscuous immune response. Additionally, the stability and flexible nature of the vaccine construct was confirmed using various molecular dynamic simulation tools. Overall, the vaccine candidate showed promising binding affinity to various HLA alleles and TLR receptors; however, further studies are needed to assess its efficacy in-vivo. In this way, we have designed a multi-subunit vaccine candidate to potentially combat and control the spread of N. gonorrhoeae.
    MeSH term(s) Molecular Dynamics Simulation ; Neisseria gonorrhoeae/genetics ; Molecular Docking Simulation ; Epitopes, B-Lymphocyte ; Epitopes, T-Lymphocyte ; Vaccines, Subunit ; Computational Biology/methods
    Chemical Substances Epitopes, B-Lymphocyte ; Epitopes, T-Lymphocyte ; Vaccines, Subunit
    Language English
    Publishing date 2023-11-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 632772-2
    ISSN 1096-1208 ; 0882-4010
    ISSN (online) 1096-1208
    ISSN 0882-4010
    DOI 10.1016/j.micpath.2023.106439
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Quest for Novel Preventive and Therapeutic Options Against Multidrug-Resistant

    Irum, Sidra / Andleeb, Saadia / Ali, Amjad / Rashid, Muhammad Ibrahim / Majid, Mahnoor

    International journal of peptide research and therapeutics

    2021  Volume 27, Issue 4, Page(s) 2313–2331

    Abstract: Pseudomonas aeruginosa: Supplementary information: The online version contains supplementary material available at 10.1007/s10989-021-10255-3. ...

    Abstract Pseudomonas aeruginosa
    Supplementary information: The online version contains supplementary material available at 10.1007/s10989-021-10255-3.
    Language English
    Publishing date 2021-08-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2192632-3
    ISSN 1573-3904 ; 1573-3149
    ISSN (online) 1573-3904
    ISSN 1573-3149
    DOI 10.1007/s10989-021-10255-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Antimicrobial Resistance and Genomic Characterization of Six New Sequence Types in Multidrug-Resistant

    Irum, Sidra / Naz, Kanwal / Ullah, Nimat / Mustafa, Zeeshan / Ali, Amjad / Arslan, Muhammad / Khalid, Kashaf / Andleeb, Saadia

    Antibiotics (Basel, Switzerland)

    2021  Volume 10, Issue 11

    Abstract: Pseudomonas ... ...

    Abstract Pseudomonas aeruginosa
    Language English
    Publishing date 2021-11-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2681345-2
    ISSN 2079-6382
    ISSN 2079-6382
    DOI 10.3390/antibiotics10111386
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Genomic Surveillance of Clinical Pseudomonas aeruginosa Isolates Reveals an Additive Effect of Carbapenemase Production on Carbapenem Resistance.

    Diorio-Toth, Luke / Irum, Sidra / Potter, Robert F / Wallace, Meghan A / Arslan, Muhammad / Munir, Tehmina / Andleeb, Saadia / Burnham, Carey-Ann D / Dantas, Gautam

    Microbiology spectrum

    2022  Volume 10, Issue 3, Page(s) e0076622

    Abstract: Carbapenem resistance in Pseudomonas aeruginosa is increasing globally, and surveillance to define the mechanisms of such resistance in low- and middle-income countries is limited. This study establishes the genotypic mechanisms of β-lactam resistance by ...

    Abstract Carbapenem resistance in Pseudomonas aeruginosa is increasing globally, and surveillance to define the mechanisms of such resistance in low- and middle-income countries is limited. This study establishes the genotypic mechanisms of β-lactam resistance by whole-genome sequencing (WGS) in 142 P. aeruginosa clinical isolates recovered from three hospitals in Islamabad and Rawalpindi, Pakistan between 2016 and 2017. Isolates were subjected to antimicrobial susceptibility testing (AST) by Kirby-Bauer disk diffusion, and their genomes were assembled from Illumina sequencing data. β-lactam resistance was high, with 46% of isolates resistant to piperacillin-tazobactam, 42% to cefepime, 48% to ceftolozane-tazobactam, and 65% to at least one carbapenem. Twenty-two percent of isolates were resistant to all β-lactams tested. WGS revealed that carbapenem resistance was associated with the acquisition of metallo-β-lactamases (MBLs) or extended-spectrum β-lactamases (ESBLs) in the
    MeSH term(s) Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Bacterial Proteins/genetics ; Carbapenems/pharmacology ; Carbapenems/therapeutic use ; Genomics ; Humans ; Imipenem/pharmacology ; Imipenem/therapeutic use ; Microbial Sensitivity Tests ; Phylogeny ; Porins/genetics ; Porins/pharmacology ; Porins/therapeutic use ; Pseudomonas Infections/drug therapy ; Pseudomonas Infections/epidemiology ; Pseudomonas aeruginosa/genetics ; Tazobactam/pharmacology ; Tazobactam/therapeutic use ; beta-Lactamases/genetics
    Chemical Substances Anti-Bacterial Agents ; Bacterial Proteins ; Carbapenems ; Porins ; Imipenem (71OTZ9ZE0A) ; beta-Lactamases (EC 3.5.2.6) ; carbapenemase (EC 3.5.2.6) ; Tazobactam (SE10G96M8W)
    Language English
    Publishing date 2022-05-31
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ZDB-ID 2807133-5
    ISSN 2165-0497 ; 2165-0497
    ISSN (online) 2165-0497
    ISSN 2165-0497
    DOI 10.1128/spectrum.00766-22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Draft Genome Sequence of a

    Irum, Sidra / Potter, Robert F / Kamran, Rubina / Mustafa, Zeeshan / Wallace, Meghan A / Burnham, C A / Dantas, Gautam / Andleeb, Saadia

    Microbiology resource announcements

    2019  Volume 8, Issue 17

    Abstract: We performed Illumina whole-genome sequencing on a carbapenem- ... ...

    Abstract We performed Illumina whole-genome sequencing on a carbapenem-resistant
    Language English
    Publishing date 2019-04-25
    Publishing country United States
    Document type Journal Article
    ISSN 2576-098X
    ISSN (online) 2576-098X
    DOI 10.1128/MRA.00107-19
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Tetracycline-inactivating enzymes from environmental, human commensal, and pathogenic bacteria cause broad-spectrum tetracycline resistance.

    Gasparrini, Andrew J / Markley, Jana L / Kumar, Hirdesh / Wang, Bin / Fang, Luting / Irum, Sidra / Symister, Chanez T / Wallace, Meghan / Burnham, Carey-Ann D / Andleeb, Saadia / Tolia, Niraj H / Wencewicz, Timothy A / Dantas, Gautam

    Communications biology

    2020  Volume 3, Issue 1, Page(s) 241

    Abstract: Tetracycline resistance by antibiotic inactivation was first identified in commensal organisms but has since been reported in environmental and pathogenic microbes. Here, we identify and characterize an expanded pool of tet(X)-like genes in environmental ...

    Abstract Tetracycline resistance by antibiotic inactivation was first identified in commensal organisms but has since been reported in environmental and pathogenic microbes. Here, we identify and characterize an expanded pool of tet(X)-like genes in environmental and human commensal metagenomes via inactivation by antibiotic selection of metagenomic libraries. These genes formed two distinct clades according to habitat of origin, and resistance phenotypes were similarly correlated. Each gene isolated from the human gut encodes resistance to all tetracyclines tested, including eravacycline and omadacycline. We report a biochemical and structural characterization of one enzyme, Tet(X7). Further, we identify Tet(X7) in a clinical Pseudomonas aeruginosa isolate and demonstrate its contribution to tetracycline resistance. Lastly, we show anhydrotetracycline and semi-synthetic analogues inhibit Tet(X7) to prevent enzymatic tetracycline degradation and increase tetracycline efficacy against strains expressing tet(X7). This work improves our understanding of resistance by tetracycline-inactivation and provides the foundation for an inhibition-based strategy for countering resistance.
    MeSH term(s) Anti-Bacterial Agents/pharmacology ; Host-Pathogen Interactions ; Humans ; Microbial Sensitivity Tests ; Pseudomonas aeruginosa/drug effects ; Pseudomonas aeruginosa/enzymology ; Symbiosis ; Tetracycline Resistance/genetics ; Tetracyclines/antagonists & inhibitors
    Chemical Substances Anti-Bacterial Agents ; Tetracyclines
    Language English
    Publishing date 2020-05-15
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-020-0966-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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