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Infect Immun, March 1998, p. 883-892, Vol. 66, No. 3
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Identification of Macrophage-Specific Infectivity Loci (mil) of Legionella pneumophila That Are Not Required for Infectivity of Protozoa

Lian-Yong Gao, Omar S. Harb, and Yousef Abu Kwaik*

Department of Microbiology and Immunology, University of Kentucky Chandler Medical Center, Lexington, Kentucky 40536-0084

Received 2 October 1997/Returned for modification 24 November 1997/Accepted 8 December 1997

We have recently shown that many mutants of Legionella pneumophila exhibit similar defective phenotypes within both U937 human-derived macrophages and the protozoan host Acanthamoeba (L.-Y. Gao, O. S. Harb, and Y. Abu Kwaik, Infect. Immun. 65:4738-4746, 1997). These observations have suggested that many of the mechanisms utilized by L. pneumophila to parasitize mammalian and protozoan cells are similar, but our data have not excluded the possibility that there are unique mechanisms utilized by L. pneumophila to survive and replicate within macrophages but not protozoa. To examine this possibility, we screened a bank of 5,280 miniTn10::kan transposon insertion mutants of L. pneumophila for potential mutants that exhibited defective phenotypes of cytopathogenicity and intracellular replication within macrophage-like U937 cells but not within Acanthamoeba polyphaga. We identified 32 mutants with various degrees of defects in cytopathogenicity, intracellular survival, and replication within human macrophages, and most of the mutants exhibited wild-type phenotypes within protozoa. Six of the mutants exhibited mild defects in protozoa. The defective loci were designated mil (for macrophage-specific infectivity loci). Based on their intracellular growth defects within macrophages, the mil mutants were grouped into five phenotypic groups. Groups I to III included the mutants that were severely defective in macrophages, while members of the other two groups exhibited a modestly defective phenotype within macrophages. The growth kinetics of many mutants belonging to groups I to III were also examined, and these were shown to have a similar defective phenotype in peripheral blood monocytes and a wild-type phenotype within another protozoan host, Hartmannella vermiformis. Transmission electron microscopy of A. polyphaga infected by three of the mil mutants belonging to groups I and II showed that they were similar to the parent strain in their capacity to recruit the rough endoplasmic reticulum (RER) around the phagosome. In contrast, infection of macrophages showed that the three mutants failed to recruit the RER around the phagosome during early stages of the infection. None of the mil mutants was resistant to NaCl, and the dot or icm NaClr mutants are severely defective within mammalian and protozoan cells. Our data indicated that in addition to differences in mechanisms of uptake of L. pneumophila by macrophages and protozoa, there were also genetic loci required for L. pneumophila to parasitize mammalian but not protozoan cells. We hypothesize that L. pneumophila has evolved as a protozoan parasite in the environment but has acquired loci specific for intracellular replication within macrophages. Alternatively, ecological coevolution with protozoa has allowed L. pneumophila to possess multiple redundant mechanisms to parasitize protozoa and that some of these mechanisms do not function within macrophages.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Kentucky Chandler Medical Center, Lexington, KY 40536-0084. Phone: (606) 323-3873. Fax: (606) 257-8994. E-mail: yabukw{at}pop.uky.edu.




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