Legionnaires’ Disease Mortality in Guinea Pigs Involves the p45 Mobile Genomic Element

Abstract

Background Legionella can cause Legionnaires’ disease, a potentially fatal form of pneumonia that occurs as sporadic epidemics. Not all strains display the same propensity to cause disease in humans. Because Legionella pneumophila serogroup 1 is responsible for >85% of infections, the majority of studies have examined this serogroup, but there are 3 commonly used laboratory strains: L pneumophila serogroup 1 Philadelphia (Phil-1)-derived strains JR32 and Lp01 and 130b-derived strain AA100. Methods We evaluated the ability of Phil-1, JR32, Lp01, and AA100 to cause disease in guinea pigs. Results We found that, although Phil-1, JR32, and AA100 cause an acute pneumonia and death by 4 days postinfection (100%), strain Lp01 does not cause mortality (0%). We also noted that Lp01 lacks a mobile element, designated p45, whose presence correlates with virulence. Transfer of p45 into Lp01 results in recovery of the ability of this strain to cause mortality, leads to more pronounced disease, and correlates with increased interferon-γ levels in the lungs and spleens before death. Conclusions These observations suggest a mechanism of Legionnaires’ disease pathogenesis due to the presence of type IVA secretion systems that cause higher mortality due to overinduction of a proinflammatory response in the host.

Legionella pneumophila p45 element influences host cell entry and sensitivity to sodium

“…Examining differences in concentrations or level of each stress could also provide insight into subtle differences between these strains that were not apparent under the conditions used in the current study. The phenotypic differences between Phil-1 and Lp01 that were not recovered by reintroduction of p45, acid resistance and pigment production, may be associated with one or more of the other known genetic differences between Lp01 and Phil-1 [31, 41]. In particular, the point mutation in the putative sensor histidine kinase luxN or the 9 bp deletion in the putative NADH dehydrogenase ndh could impact these phenotypic characteristics.…”

Increased DNA methylation, cellular senescence and premature epigenetic aging in guinea pigs and humans with tuberculosis

“…The animals were maintained with commercial diet and water ad libitum. The guinea pigs were divided into two groups of four, one group underwent aerosol infection with Mtb strain CDC1551, grown as described previously [ 41 , 42 ] and washed with saline and suspended at an OD 600 of 0.1 prior to nebulization using a Madison chamber, as described previously [ 41 , 43 ]. The other group was used as a control without any infection procedure.…”

Molecular regulation of virulence in Legionella pneumophila

“…Two CsrA paralogs, since renamed CsrR ( lpg1593 ) and CsrT ( lpg2057 ), have been investigated whereas the third csrA‐22 ( lpg1003 ) has limited information at present. A fourth ICE‐related csrA paralog, lvrC/lpg1257 , is present in the L. pneumophila Philadelphia‐1 progenitor strain but has been lost along with the lvr region of the P45 genomic island in the Lp01/Lp02 derivative strains (Christensen et al., 2019a, 2019b; Rao et al., 2013; Wee et al., 2013). CsrR is under the regulation of CsrA and IHF, and functions as an RNA‐binding protein necessary for optimal persistence in water (Abbott et al., 2015b; Ge et al., 2019).…”