OR04
Host-pathogen co-adaptation shapes susceptibility to infection with M. tuberculosis
M I Groeschel(1) J Perez-Ilanos(6) V Escuyer(3) K Musser(3) J Meissner(4) P Kouw(2) R Diel(5) S Homolka(6) D van Soolingen(7) S Niemann(6) S Ahuja(4) M R Farhat(1)
1:Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA; 2:Public Health Service Amsterdam, The Netherlands; 3:Wadsworth Center, New York State Department of Health, Albany, New York, USA; 4:New York City Department of Health and Mental Hygiene, Bureau of Tuberculosis Control, Queens, New York; 5:Institute for Epidemiology, University Medical Hospital Schleswig-Holstein, Kiel, Germany; 6:Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany; 7:National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
The study of evolution of host-pathogen relationships is fundamental to understanding the emergence and control of infectious diseases. The obligate human pathogen M. tuberculosis (Mtb) demonstrates genetic lineages that are geographically restricted and may be differentially transmissible patient-to-patient. Based on these observations, Mtb’s geographically restricted lineages have been hypothesized to be niche specialists that preferentially infect local human subpopulations. However, the lack of contact tracing data directly measuring transmissibility in cosmopolitan societies with mixing of human and pathogen populations has hindered the study of naturally occurring co-adaptation in Mtb. Here, using a multi-site cohort of tuberculosis index cases with pathogen sequence data and linked social contacts, we show that specialist Mtb lineages L1,L2spec,L3,L4spec,L5,L6 are intrinsically less transmissible than generalist Mtb lineages (L2gen,L4gen) across Western European and North American populations. Comparing transmissibility between sympatric and allopatric host-pathogen pairs, we found the first controlled evidence for co-adaptation between Mtb and its human host; sympatric host-pathogen exposures had 1.47 time the odds of transmission compared with allopatric exposures. Furthermore, we measured increased phagocytosis and growth rates in sympatric infections of European and African macrophages in vitro. Although the current Mtb epidemic is driven by highly successful generalist Mtb lineages, long term co-adaptation between Mtb and humans has resulted in differential transmissibility between allopatric and sympatric hosts for a specialist subset of lineages. Understanding the specific genetic and immunological underpinnings of this co-adaptation can inform rational vaccine design and TB control.