Guest guest Posted January 5, 2006 Report Share Posted January 5, 2006 This paper is of vast importance to the fine science of microbicide. To see why, start out by reading the beginning of the Discussion. This is free online full text. I'm not in a real disciplined mood here but the controls and rationale in this paper seem tight... one possible shortcoming is well-addressed by the authors in the final few sentences of the Results. Also problematic is the assumption that all forms of the organism are capable of replication in order to form colonies in the CFU assay. This may be a huge problem. See PMID 15548322. I think so, but I am not quite sure whether MTB infection is clinically pathogenic in the mice they used (the " normal " ones, not the IFNg knockouts which MTB easily kills). This " stalemate " finding will be much more significant to me if MTB is indeed pathogenic to wild-type mice. On the other hand, the existence of a stalemate involving a subclinical infection would not be surprising - because such a stalemate is not very harmful to the host - and would be much less suggestive reguarding the question of what is going on in our diseases and their treatment. ====================================================== Infect Immun. 2005 Jan;73(1):546-51. Related Articles, Links Replication dynamics of Mycobacterium tuberculosis in chronically infected mice. Munoz-Elias EJ, Timm J, Botha T, Chan WT, Gomez JE, McKinney JD. Laboratory of Infection Biology, The Rockefeller University, 1230 York Ave., New York, NY 10021, USA. The dynamics of host-pathogen interactions have important implications for the design of new antimicrobial agents to treat chronic infections such as tuberculosis (TB), which is notoriously refractory to conventional drug therapy. In the mouse model of TB, an acute phase of exponential bacterial growth in the lungs is followed by a chronic phase characterized by relatively stable numbers of bacteria. This equilibrium could be static, with little ongoing replication, or dynamic, with continuous bacterial multiplication balanced by bacterial killing. A static model predicts a close correspondence between " viable counts " (live bacteria) and " total counts " (live plus dead bacteria) in the lungs over time. A dynamic model predicts the divergence of total counts and viable counts over time due to the accumulation of dead bacteria. Here, viable counts are defined as bacterial CFU enumerated by plating lung homogenates; total counts are defined as bacterial chromosome equivalents (CEQ) enumerated by using quantitative real-time PCR. We show that the viable and total bacterial counts in the lungs of chronically infected mice do not diverge over time. Rapid degradation of dead bacteria is unlikely to account for the stability of bacterial CEQ numbers in the lungs over time, because treatment of mice with isoniazid for 8 weeks led to a marked reduction in the number of CFU without reducing the number of CEQ. These observations support the hypothesis that the stable number of bacterial CFU in the lungs during chronic infection represents a static equilibrium between host and pathogen. PMID: 15618194 [PubMed - indexed for MEDLINE] Quote Link to comment Share on other sites More sharing options...
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