Minimum inhibitory concentration (MIC) distribution among wild-type strains of Legionella pneumophila identifies a subpopulation with reduced susceptibility to macrolides owing to efflux pump genes

Vandewalle-Capo, Marine; Massip, Clémence; Descours, Ghislaine; Charavit, Joséphine; Chastang, Joëlle; Billy, Pierre Alain; Boisset, Sandrine; Lina, Gérard; Gilbert, Christophe; Maurin, Max; Jarraud, Sophie; Ginevra, Christophe

doi:10.1016/j.ijantimicag.2017.08.001

Cited by 42 publications

(52 citation statements)

References 17 publications

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“…Within the context of gene enrichment, two recent studies [ 41 , 42 ] identified an efflux pump (LpeAB) found primarily in ST1 strains that confers increased macrolide resistance in Legionella . We detected the genes encoding this pump in 501 ST1 and ST1-like isolate sequences in the current dataset and no enrichment was found for one or more particular ST1 subgroup.…”

Section: Resultsmentioning

confidence: 99%

Genomic heterogeneity differentiates clinical and environmental subgroups of Legionella pneumophila sequence type 1

et al. 2018

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Legionella spp. are the cause of a severe bacterial pneumonia known as Legionnaires’ disease (LD). In some cases, current genetic subtyping methods cannot resolve LD outbreaks caused by common, potentially endemic L. pneumophila (Lp) sequence types (ST), which complicates laboratory investigations and environmental source attribution. In the United States (US), ST1 is the most prevalent clinical and environmental Lp sequence type. In order to characterize the ST1 population, we sequenced 289 outbreak and non-outbreak associated clinical and environmental ST1 and ST1-variant Lp strains from the US and, together with international isolate sequences, explored their genetic and geographic diversity. The ST1 population was highly conserved at the nucleotide level; 98% of core nucleotide positions were invariant and environmental isolates unassociated with human disease (n = 99) contained ~65% more nucleotide diversity compared to clinical-sporadic (n = 139) or outbreak-associated (n = 28) ST1 subgroups. The accessory pangenome of environmental isolates was also ~30–60% larger than other subgroups and was enriched for transposition and conjugative transfer-associated elements. Up to ~10% of US ST1 genetic variation could be explained by geographic origin, but considerable genetic conservation existed among strains isolated from geographically distant states and from different decades. These findings provide new insight into the ST1 population structure and establish a foundation for interpreting genetic relationships among ST1 strains; these data may also inform future analyses for improved outbreak investigations.

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Section: Resultsmentioning

confidence: 99%

Genomic heterogeneity differentiates clinical and environmental subgroups of Legionella pneumophila sequence type 1

et al. 2018

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“…In addition, Vandewalle-Capo et al . 49 demonstrated that the reduced azithromycin susceptibility of ST1 strains was linked to the presence of these lpeAB genes. In our study, we found significant differences in resistance to azithromycin between co-localized genotypes, especially Gt4 and Gt6 strains, both belonging to ST1 (Fig.…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial agent susceptibilities of Legionella pneumophila MLVA-8 genotypes

Sharaby

Nitzan

Brettar

et al. 2019

Sci Rep

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Legionella pneumophila causes human lung infections resulting in severe pneumonia. High-resolution genotyping of L. pneumophila isolates can be achieved by multiple-locus variable-number tandem-repeat analysis (MLVA-8). Legionella infections in humans occur as a result of inhalation of bacteria-containing aerosols, thus, our aim was to study the antimicrobial susceptibilities of different MLVA-8 genotypes to ten commonly used antimicrobial agents in legionellosis therapy. Epidemiological cut-off values were determined for all antibiotics. Significant differences were found between the antimicrobial agents’ susceptibilities of the three studied environmental genotypes (Gt4, Gt6, and Gt15). Each genotype exhibited a significantly different susceptibility profile, with Gt4 strains (Sequence Type 1) significantly more resistant towards most studied antimicrobial agents. In contrast, Gt6 strains (also Sequence Type 1) were more susceptible to six of the ten studied antimicrobial agents compared to the other genotypes. Our findings show that environmental strains isolated from adjacent points of the same water system, exhibit distinct antimicrobial resistance profiles. These differences highlight the importance of susceptibility testing of Legionella strains. In Israel, the most extensively used macrolide for pneumonia is azithromycin. Our results point at the fact that clarithromycin (another macrolide) and trimethoprim with sulfamethoxazole (SXT) were the most effective antimicrobial agents towards L. pneumophila strains. Moreover, legionellosis can be caused by multiple L. pneumophila genotypes, thus, the treatment approach should be the use of combined antibiotic therapy. Further studies are needed to evaluate specific antimicrobial combinations for legionellosis therapy.

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“…pascullei strain U8W, respectively (15). In silico MLST identified the isolates as sequence type 1 (ST1) (11, 12), and gene annotation confirmed the presence of the lpeAB genes encoding a macrolide efflux pump, which confers reduced sensitivity to azithromycin (17, 18).…”

Section: Announcementmentioning

confidence: 97%

Draft Genome Sequences of Seven Legionella pneumophila Isolates from a Hot Water System of a Large Building

Gomez-Alvarez

Boczek

King

et al. 2019

Microbiol Resour Announc

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Minimum inhibitory concentration (MIC) distribution among wild-type strains of Legionella pneumophila identifies a subpopulation with reduced susceptibility to macrolides owing to efflux pump genes

Cited by 42 publications

References 17 publications

Genomic heterogeneity differentiates clinical and environmental subgroups of Legionella pneumophila sequence type 1

Genomic heterogeneity differentiates clinical and environmental subgroups of Legionella pneumophila sequence type 1

Antimicrobial agent susceptibilities of Legionella pneumophila MLVA-8 genotypes

Draft Genome Sequences of Seven Legionella pneumophila Isolates from a Hot Water System of a Large Building

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