Antibiotic-resistant S. aureus infections are now increasingly encountered in the community. These community-based infections, especially those due to methicillin-resistant S. aureus (MRSA), have occurred in groups without the usual risk factors. There is minimal understanding of how these strains spread and subsequently become established within communities. This remains a critical issue if interventions are to be designed to prevent population level dissemination of community-associated (CA)-MRSA isolates. This study will address the following questions. 1. What pressures are responsible for the pathways of CA-MRSA spread within the community? Patterns of CA-MRSA transmission within the Columbia University Medical Center catchment area, a largely underserved immigrant population, will be identified. The study will use a retrospective, case control study design. lndex cases with a documented CA-MRSA infection and community matched index controls will provide information on both themselves and their egocentric network members. Network information will be supplemented with data collected from potential reservoirs of CA-MRSA within the community (e.g., daycare facilities and schools). Subjects at these sites will be anonymously sampled for colonization/infection with CA-MRSA. The results will be used to create estimates of transmission probabilities for individual, network and community parameters. A mathematical model will then be developed to simulate transmission pathways within the community, as well as investigate potential intervention strategies that might be used to prevent CA-MRSA transmission. 2. Do strains of S. aureus evolve in the community and become more adapted to the environment? We hypothesize that CA-MRSA strains adapt to their environment and become more ecologically """"""""fit"""""""" as they spread. Selected strains prevalent in the community among different subgroups of the population (e.g., children at daycare) will undergo genetic analysis using comparative total genome sequencing. Mutations that might enhance fitness will be screened using parameters such as growth rate, adherence to different tissue surfaces and survival on environmental surfaces. Screens for the """"""""fitness"""""""" mutations will then be carried out on all S. aureus strains collected from the community. This proposal examines the spread of CA-MRSA in an inner city population. Our recently completed CDC study demonstrated that the community is interested and willing to participate in these types of investigations. Unlike other communities in the United States, CA-MRSA has only recently begun to emerge as a prominent pathogen in this community so that transmission studies are still possible, before CA-MRSA becomes endemic. Finally, this investigation is an innovative integration of diverse research methods including social network data collection strategies, molecular epidemiology, genetic strain analysis and mathematical modeling to address this pressing issue. The end result should be a more comprehensive understanding of CA-MRSA transmission and the intervention strategies that are most likely to be successful in a community setting.

Public Health Relevance

There is minimal understanding of how community-associated methicillin-resistant S. aureus (CA-MRSA) spreads and subsequently become established within communities. The goals of this study are to: 1) identify the social network contacts as well as the nature of contacts of CA-MRSA infected subjects and the potential environmental reservoirs of CA-MRSA;2) develop a mathematical model that predicts transmission pathways and potential intervention strategies within the community;and 3) define the role of adaptive genetic changes in fitness of CA-MRSA strains on transmission.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Huntley, Clayton C
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Columbia University (N.Y.)
Internal Medicine/Medicine
Schools of Medicine
New York
United States
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Uhlemann, Anne-Catrin; McAdam, Paul R; Sullivan, Sean B et al. (2017) Evolutionary Dynamics of Pandemic Methicillin-Sensitive Staphylococcus aureus ST398 and Its International Spread via Routes of Human Migration. MBio 8:
Knox, Justin; Sullivan, Sean B; Urena, Julia et al. (2016) Association of Environmental Contamination in the Home With the Risk for Recurrent Community-Associated, Methicillin-Resistant Staphylococcus aureus Infection. JAMA Intern Med 176:807-15
Knox, Justin; Uhlemann, Anne-Catrin; Lowy, Franklin D (2015) Staphylococcus aureus infections: transmission within households and the community. Trends Microbiol 23:437-44
Knox, J; Van Rijen, M; Uhlemann, A-C et al. (2015) Community-associated methicillin-resistant Staphylococcus aureus transmission in households of infected cases: a pooled analysis of primary data from three studies across international settings. Epidemiol Infect 143:354-65
Uhlemann, Anne-Catrin; Lowy, Franklin D (2014) Reply to Gandra et al. Clin Infect Dis 58:307-8
Uhlemann, Anne-Catrin; Otto, Michael; Lowy, Franklin D et al. (2014) Evolution of community- and healthcare-associated methicillin-resistant Staphylococcus aureus. Infect Genet Evol 21:563-74
Uhlemann, Anne-Catrin; Hafer, Cory; Miko, Benjamin A et al. (2013) Emergence of sequence type 398 as a community- and healthcare-associated methicillin-susceptible staphylococcus aureus in northern Manhattan. Clin Infect Dis 57:700-3
David, Michael Z; Siegel, Jane; Lowy, Franklin D et al. (2013) Asymptomatic carriage of sequence type 398, spa type t571 methicillin-susceptible Staphylococcus aureus in an urban jail: a newly emerging, transmissible pathogenic strain. J Clin Microbiol 51:2443-7
Hafer, Cory; Lin, Ying; Kornblum, John et al. (2012) Contribution of selected gene mutations to resistance in clinical isolates of vancomycin-intermediate Staphylococcus aureus. Antimicrob Agents Chemother 56:5845-51
Knox, Justin; Uhlemann, Anne-Catrin; Miller, Maureen et al. (2012) Environmental contamination as a risk factor for intra-household Staphylococcus aureus transmission. PLoS One 7:e49900

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