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  • 1
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    Online Resource
    Rapid Growth of Uropathogenic Escherichia coli during Human Urinary Tract Infection
    American Society for Microbiology ; 2018
    In:  mBio Vol. 9, No. 2 ( 2018-05-02)
    Details
    In: mBio, American Society for Microbiology, Vol. 9, No. 2 ( 2018-05-02)
    Abstract: Uropathogenic Escherichia coli (UPEC) strains cause most urinary tract infections in otherwise healthy women. While we understand numerous virulence factors are utilized by E. coli to colonize and persist within the urinary tract, these properties are inconsequential unless bacteria can divide rapidly and survive the host immune response. To determine the contribution of growth rate to successful colonization and persistence, we employed two methods: one involving the segregation of a nonreplicating plasmid in bacteria as they divide and the peak-to-trough ratio, a sequencing-based method that enumerates chromosomal replication forks present during cell division. We found that UPEC strains divide extraordinarily rapidly during human UTIs. These techniques will be broadly applicable to measure in vivo growth rates of other bacterial pathogens during host colonization.
    Type of Medium: Online Resource
    ISSN: 2161-2129 , 2150-7511
    URL: Article
    DOI: 10.1128/mBio.00186-18
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2018
    detail.hit.zdb_id: 2557172-2
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  • 2
    Online Resource
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    Outbreak of Murine Infection with Clostridium difficile Associated with the Administration of a Pre- and Perinatal Methyl Donor Diet
    American Society for Microbiology ; 2019
    In:  mSphere Vol. 4, No. 2 ( 2019-04-24)
    Details
    In: mSphere, American Society for Microbiology, Vol. 4, No. 2 ( 2019-04-24)
    Abstract: Between October 2016 and June 2017, a C57BL/6J mouse colony that was undergoing a pre- and perinatal methyl donor supplementation diet intervention to study the impact of parental nutrition on offspring susceptibility to disease was found to suffer from an epizootic of unexpected deaths. Necropsy revealed the presence of severe colitis, and further investigation linked these outbreak deaths to a Clostridium difficile strain of ribotype 027 that we term 16N203. C. difficile infection (CDI) is associated with antibiotic use in humans. Current murine models of CDI rely on antibiotic pretreatment to establish clinical phenotypes. In this report, the C. difficile outbreak occurs in F1 mice linked to alterations in the parental diet. The diagnosis of CDI in the affected mice was confirmed by cecal/colonic histopathology, the presence of C. difficile bacteria in fecal/colonic culture, and detection of C. difficile toxins. F1 mice from parents fed the methyl supplementation diet also had significantly reduced survival ( P 〈 0.0001) compared with F1 mice from parents fed the control diet. When we tested the 16N203 outbreak strain in an established mouse model of antibiotic-induced CDI, we confirmed that this strain is pathogenic. Our serendipitous observations from this spontaneous outbreak of C. difficile in association with a pre- and perinatal methyl donor diet suggest the important role that diet may play in host defense and CDI risk factors. IMPORTANCE Clostridium difficile infection (CDI) has become the leading cause of infectious diarrhea in hospitals worldwide, owing its preeminence to the emergence of hyperendemic strains, such as ribotype 027 (RT027). A major CDI risk factor is antibiotic exposure, which alters gut microbiota, resulting in the loss of colonization resistance. Current murine models of CDI also depend on pretreatment of animals with antibiotics to establish disease. The outbreak that we report here is unique in that the CDI occurred in mice with no antibiotic exposure and is associated with a pre- and perinatal methyl supplementation donor diet intervention study. Our investigation subsequently reveals that the outbreak strain that we term 16N203 is an RT027 strain, and this isolated strain is also pathogenic in an established murine model of CDI (with antibiotics). Our report of this spontaneous outbreak offers additional insight into the importance of environmental factors, such as diet, and CDI susceptibility.
    Type of Medium: Online Resource
    ISSN: 2379-5042
    URL: Article
    DOI: 10.1128/mSphereDirect.00138-19
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2019
    detail.hit.zdb_id: 2844248-9
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  • 3
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    Combined comparative genomics and clinical modeling reveals plasmid-encoded genes are independently associated with Klebsiella infection
    Springer Science and Business Media LLC ; 2022
    In:  Nature Communications Vol. 13, No. 1 ( 2022-08-01)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2022-08-01)
    Abstract: Members of the Klebsiella pneumoniae species complex frequently colonize the gut and colonization is associated with subsequent infection. To identify genes associated with progression from colonization to infection, we undertook a case-control comparative genomics study. Concordant cases ( N  = 85), where colonizing and invasive isolates were identical strain types, were matched to asymptomatically colonizing controls ( N  = 160). Thirty-seven genes are associated with infection, 27 of which remain significant following adjustment for patient variables and bacterial phylogeny. Infection-associated genes are not previously characterized virulence factors, but instead a diverse group of stress resistance, regulatory and antibiotic resistance genes, despite careful adjustment for antibiotic exposure. Many genes are plasmid borne, and for some, the relationship with infection is mediated by gut dominance. Five genes were validated in a geographically-independent cohort of colonized patients. This study identifies several genes reproducibly associated with progression to infection in patients colonized by diverse Klebsiella .
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-022-31990-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2553671-0
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  • 4
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    Whole Genome Sequencing—Implications for Infection Prevention and Outbreak Investigations
    Springer Science and Business Media LLC ; 2017
    In:  Current Infectious Disease Reports Vol. 19, No. 4 ( 2017-4)
    Details
    In: Current Infectious Disease Reports, Springer Science and Business Media LLC, Vol. 19, No. 4 ( 2017-4)
    Type of Medium: Online Resource
    ISSN: 1523-3847 , 1534-3146
    URL: Article
    DOI: 10.1007/s11908-017-0570-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2094167-5
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  • 5
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    Cohorting KPC+ Klebsiella pneumoniae (KPC-Kp)–positive patients: A genomic exposé of cross-colonization hazards in a long-term acute-care hospital (LTACH)
    Cambridge University Press (CUP) ; 2020
    In:  Infection Control & Hospital Epidemiology Vol. 41, No. 10 ( 2020-10), p. 1162-1168
    Details
    In: Infection Control & Hospital Epidemiology, Cambridge University Press (CUP), Vol. 41, No. 10 ( 2020-10), p. 1162-1168
    Abstract: Cohorting patients who are colonized or infected with multidrug-resistant organisms (MDROs) protects uncolonized patients from acquiring MDROs in healthcare settings. The potential for cross transmission within the cohort and the possibility of colonized patients acquiring secondary isolates with additional antibiotic resistance traits is often neglected. We searched for evidence of cross transmission of KPC+ Klebsiella pneumoniae (KPC-Kp) colonization among cohorted patients in a long-term acute-care hospital (LTACH), and we evaluated the impact of secondary acquisitions on resistance potential. Design: Genomic epidemiological investigation. Setting: A high-prevalence LTACH during a bundled intervention that included cohorting KPC-Kp–positive patients. Methods: Whole-genome sequencing (WGS) and location data were analyzed to identify potential cases of cross transmission between cohorted patients. Results: Secondary KPC-Kp isolates from 19 of 28 admission-positive patients were more closely related to another patient’s isolate than to their own admission isolate. Of these 19 cases, 14 showed strong genomic evidence for cross transmission ( 〈 10 single nucleotide variants or SNVs), and most of these patients occupied shared cohort floors (12 patients) or rooms (4 patients) at the same time. Of the 14 patients with strong genomic evidence of acquisition, 12 acquired antibiotic resistance genes not found in their primary isolates. Conclusions: Acquisition of secondary KPC-Kp isolates carrying distinct antibiotic resistance genes was detected in nearly half of cohorted patients. These results highlight the importance of healthcare provider adherence to infection prevention protocols within cohort locations, and they indicate the need for future studies to assess whether multiple-strain acquisition increases risk of adverse patient outcomes.
    Type of Medium: Online Resource
    ISSN: 0899-823X , 1559-6834
    URL: Article
    DOI: 10.1017/ice.2020.261
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2106319-9
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  • 6
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    1247. Genomic Epidemiology of MRSA DURING Incarceration at a Large Inner-City Jail
    Oxford University Press (OUP) ; 2018
    In:  Open Forum Infectious Diseases Vol. 5, No. suppl_1 ( 2018-11-26), p. S379-S379
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 5, No. suppl_1 ( 2018-11-26), p. S379-S379
    Abstract: Congregate settings may facilitate spread of USA300. Jails may be a location where individuals already colonized with MRSA (from preceding exposures) intermingle with others, potentially augmenting spread. We examined the rate of MRSA acquisition during incarceration and characterized the genomic epidemiology of MRSA strains entering the jail, MRSA acquisition isolates, and archived (2015–2017) clinical MRSA isolates from male detainees. Methods Males incarcerated at the Cook County Jail were enrolled within 72 hours of intake and surveillance cultures for MRSA carriage (nares, throat, groin) collected. Detainees in jail at Day 30 had cultures repeated to determine MRSA acquisition. A survey was administered and chart review performed to identify predictors of acquisition. Whole-genome sequencing and phylogenetic analysis of isolates were performed with integration of epidemiologic data. Results 800 males were enrolled, with 19% colonized with MRSA at jail intake. 143 reached the Day30 visit (82% AA, 7% Hispanic), by which there were 12 MRSA acquisitions detected. Heroin use before entering the jail (OR 3.67, P = 0.04) and sharing personal items during incarceration (OR = 4.92, P = .01) were significant predictors of acquisition. Sequenced clinical isolates (n = 175) (largely skin infections) were more likely to resemble each other genetically than the diverse intake strains (P & lt; 0.001) (figure), suggesting clinical isolates may originate from transmission within the jail or be due to more virulent strains. 7/12 (58%) acquisition isolates were within 40 SNVs from another isolate; five were genomically similar to intake isolates and two were similar to clinical isolates. Acquisition strains from those sharing personal items (vs. not) tended to have closer relatedness (19 SNVs vs. 56 SNVs, P = 0.22). Conclusion There is a high burden of MRSA entering jail. Genomic analysis of acquisition and clinical isolates suggests potential spread of incoming strains and possible networks spread of prevalent strains during incarceration. Sharing of personal items during incarceration is associated with MRSA acquisition and could be a focus of an intervention. Future study of epidemiologic and location data may inform targeting of interventions within the jail. Disclosures All authors: No reported disclosures.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofy210.1080
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2757767-3
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  • 7
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    159. Genomic Epidemiology of MRSA at Intake to a Large Inner-City Jail: Evidence for Community Transmission Networks?
    Oxford University Press (OUP) ; 2018
    In:  Open Forum Infectious Diseases Vol. 5, No. suppl_1 ( 2018-11-26), p. S13-S14
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 5, No. suppl_1 ( 2018-11-26), p. S13-S14
    Abstract: USA300 is endemic in the community, with congregate settings potentially facilitating spread. The impact of community MRSA transmission networks on importation of MRSA into urban jails is unknown. We examined MRSA colonization isolates entering the jail and determined whether there are community transmission networks for MRSA that precede incarceration. Methods HIV-infected and HIV-negative males incarcerated at the Cook County Jail were enrolled within 72 hours of intake. Surveillance cultures (nares, throat, and groin) were collected to determine prevalence of MRSA colonization. A survey was administered to identify predictors of colonization. Whole-genome sequencing (WGS) and phylogenetic analysis were integrated with epidemiologic data to identify community transmission networks. Results A total of 800 males were enrolled (83% AA and 9% Hispanic); 58% were HIV-infected. The prevalence of MRSA colonization at intake was 19%. In multivariate analysis, methamphetamine use (METH), unstable housing, and prior jail incarceration were significant predictors of MRSA. Among HIV patients, injection drug use and HIV care at outpatient Clinic A that emphasize comprehensive care to the LGBTQ community were significant predictors of MRSA. Of the 31 (45%) patients with care at Clinic A, 14 had MRSA colonization. We sequenced 145 isolates from unique individuals, with 102 and 13 closely related to USA300 and USA500 reference genomes, respectively. USA300 strains from intake were diverse (median pairwise SNV distance = 109), with several small clusters noted. WGS revealed the high prevalence of MRSA in Clinic A was not due to clonal spread but rather an intermingling of distinct community transmission networks (strains were highly diverse; median pairwise SNV distance = 410). We did identify a 13-member community transmission network underlying spread of USA500 (figure). Members of this network were more likely to be HIV-infected (P & lt; 0.004), MSM (P & lt; 0.001), and METH (P & lt; 0.001). Conclusion A high proportion of individuals enter jail already colonized with MRSA and colonization risk factors provide clues to community reservoirs for MRSA. WGS extended epidemiologic analysis and revealed community transmission networks that could be a potential focus for an intervention. Disclosures All authors: No reported disclosures.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofy209.029
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2757767-3
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  • 8
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    Online Resource
    Relatedness of MRSA and VRE Strains Isolated from Post-acute Care Patients and Their Environment: a Longitudinal Assessment
    Oxford University Press (OUP) ; 2017
    In:  Open Forum Infectious Diseases Vol. 4, No. suppl_1 ( 2017), p. S639-S639
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 4, No. suppl_1 ( 2017), p. S639-S639
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofx163.1696
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2017
    detail.hit.zdb_id: 2757767-3
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  • 9
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    Online Resource
    Metabolic Network Model of a Human Oral Pathogen
    American Society for Microbiology ; 2009
    In:  Journal of Bacteriology Vol. 191, No. 1 ( 2009-01), p. 74-90
    Details
    In: Journal of Bacteriology, American Society for Microbiology, Vol. 191, No. 1 ( 2009-01), p. 74-90
    Abstract: The microbial community present in the human mouth is engaged in a complex network of diverse metabolic activities. In addition to serving as energy and building-block sources, metabolites are key players in interspecies and host-pathogen interactions. Metabolites are also implicated in triggering the local inflammatory response, which can affect systemic conditions such as atherosclerosis, obesity, and diabetes. While the genome of several oral pathogens has been sequenced, quantitative understanding of the metabolic functions of any oral pathogen at the system level has not been explored yet. Here we pursue the computational construction and analysis of the genome-scale metabolic network of Porphyromonas gingivalis , a gram-negative anaerobe that is endemic in the human population and largely responsible for adult periodontitis. Integrating information from the genome, online databases, and literature screening, we built a stoichiometric model that encompasses 679 metabolic reactions. By using flux balance approaches and automated network visualization, we analyze the growth capacity under amino-acid-rich medium and provide evidence that amino acid preference and cytotoxic by-product secretion rates are suitably reproduced by the model. To provide further insight into the basic metabolic functions of P. gingivalis and suggest potential drug targets, we study systematically how the network responds to any reaction knockout. We focus specifically on the lipopolysaccharide biosynthesis pathway and identify eight putative targets, one of which has been recently verified experimentally. The current model, which is amenable to further experimental testing and refinements, could prove useful in evaluating the oral microbiome dynamics and in the development of novel biomedical applications.
    Type of Medium: Online Resource
    ISSN: 0021-9193 , 1098-5530
    URL: Article
    DOI: 10.1128/JB.01123-08
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2009
    detail.hit.zdb_id: 1481988-0
    SSG: 12
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  • 10
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    Genetic Determinants of Trehalose Utilization Are Not Associated With Severe Clostridium difficile Infection Outcome
    Oxford University Press (OUP) ; 2020
    In:  Open Forum Infectious Diseases Vol. 7, No. 1 ( 2020-01-01)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 7, No. 1 ( 2020-01-01)
    Abstract: In a case–control study of patients with Clostridium difficile infection, we found no statistically significant association between the presence of trehalose utilization variants in infecting C. difficile strains and development of severe infection outcome. These results do not support trehalose utilization conferring enhanced virulence in the context of human C. difficile infections.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofz548
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2757767-3
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