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Biomedical subjects

Jean-Marc Rolain

Publications and source records attributed to Jean-Marc Rolain.

At least 19 recordsLinked to original sources

Global lessons from antibiotic resistance: Metformin-hydrolysing genes in transposable elements, a new threat for type II diabetic patients?

OBJECTIVES: To investigate the evolutionary origin, genomic mobility, and potential dissemination of metformin-hydrolysing genes (mfmAB), and to assess whether environmental selection by metformin pollution may drive the emergence of transferable pharmaceutical-degrading traits analogous to antibiotic resistance. METHODS: Large-scale comparative genomics was performed using publicly available bacterial genomes carrying mfmAB homologs. Phylogenomic reconstruction, average nucleotide identity analysis, genomic context comparison, plasmid characterization, and insertion sequence mapping were used to infer evolutionary history and identify mechanisms of horizontal gene transfer. RESULTS: mfmAB homologs were identified in twelve Aminobacter and three Pseudomonas genomes within a conserved ∼8.2 kb gene cluster. Phylogenomic analyses showed that metformin-degrading capacity emerged independently in multiple Aminobacter lineages across distinct continents, consistent with convergent evolution under anthropogenic selective pressure. Genomic comparisons indicated a chromosomal origin of mfmAB, followed by mobilization onto conjugative plasmids through IS1182-mediated transposition. In Pseudomonas, additional IS3/IS6-mediated transposition events integrated mfmAB into diverse plasmid backbones, frequently within composite transposons also encoding guanylurea and biguanide degradation pathways (guuH, bguH). These findings reveal a dynamic modular assembly of metabolic functions facilitating adaptation to pharmaceutical pollutants. CONCLUSIONS: Metformin pollution appears to promote the emergence and mobilization of pharmaceutical-degrading genes through mechanisms paralleling antibiotic resistance evolution. Although no clinical impact has yet been demonstrated, the potential spread of such genes into human-associated microbiomes and their possible co-selection with antibiotic resistance determinants represent an emerging One Health concern. Environmental surveillance of pharmaceutical-degrading genes is warranted to anticipate future threats to drug efficacy.

Convergent evolution↗

Increased levels of soluble CD40L in African tick bite fever: possible involvement of TLRs in the pathogenic interaction between Rickettsia africae, endothelial cells, and platelets.

The pathophysiological hallmark of spotted fever group rickettsioses comprises infection of endothelial cells with subsequent infiltration of inflammatory cells. Based on its ability to promote inflammation and endothelial cell activation, we investigated the role of CD40L in African tick bite fever (ATBF), caused by Rickettsia africae, using different experimental approaches. Several significant findings were revealed. 1) Patients with ATBF (n = 15) had increased serum levels of soluble CD40 ligand (sCD40L), which decreased during follow-up. 2) These enhanced sCD40L levels seem to reflect both direct and indirect (through endothelial cell activation involving CX3CL1-related mechanisms) effects of R. africae on platelets. 3) In combination with sCD40L, R. africae promoted a procoagulant state in endothelial cells by up-regulating tissue factor and down-regulating thrombomodulin expression. 4) Although the R. africae-mediated activation of platelets involved TLR2, the combined procoagulant effects of R. africae and sCD40L on endothelial cells involved TLR4. 5) Doxycycline counteracted the combined procoagulant effects of R. africae and sCD40L on endothelial cells. Our findings suggest an inflammatory interaction between platelets and endothelial cells in ATBF, involving TLR-related mechanisms. This interaction, which includes additive effects between sCD40L and R. africae, may contribute to endothelial inflammation and hypercoagulation in this disorder.

Adult↗

Molecular characterization of resistance to macrolides in Bartonella henselae.

We selected in vitro erythromycin-resistant strains of Bartonella henselae. The mutants obtained had point mutations in domain V of 23S rRNA and/or in ribosomal protein L4. One lymph node of a patient with cat-scratch disease had such a mutation in 23S rRNA, suggesting that natural resistant strains may infect humans.

Bartonella henselae↗

First isolation of Bartonella alsatica from a valve of a patient with endocarditis.

We report the first documented case of endocarditis in a man infected with Bartonella alsatica, which causes bacteremia in healthy wild rabbits. B. alsatica was identified by serology and culture and by PCR of an aortic valve specimen. B. alsatica should be added to the list of zoonotic agents of blood culture-negative endocarditis.

Aged↗

Rickettsia felis infection, Tunisia.

We report, for the first time, serologic evidence of Rickettsia felis and R. aeschlimannii infections acquired in Tunisia from 1998 to 2003. We found that most patients with antibodies against both R. conorii and R. typhi had serologic evidence of R. felis infection.

Humans↗

Rickettsial infections and fever, Vientiane, Laos.

Rickettsial diseases have not been described previously from Laos, but in a prospective study, acute rickettsial infection was identified as the cause of fever in 115 (27%) of 427 adults with negative blood cultures admitted to Mahosot Hospital in Vientiane, Laos. The organisms identified by serologic analysis were Orientia tsutsugamushi (14.8%), Rickettsia typhi (9.6%), and spotted fever group rickettsia (2.6% [8 R. helvetica, 1 R. felis, 1 R. conorii subsp. indica, and 1 Rickettsia "AT1"]). Patients with murine typhus had a lower frequency of peripheral lymphadenopathy than those with scrub typhus (3% vs. 46%, p<0.001). Rickettsioses are an underrecognized cause of undifferentiated febrile illnesses among adults in Laos. This finding has implications for the local empiric treatment of fever.

Adolescent↗

"Candidatus Rickettsia kellyi," India.

We report the first laboratory-confirmed human infection due to a new rickettsial genotype in India, "Candidatus Rickettsia kellyi," in a 1-year-old boy with fever and maculopapular rash. The diagnosis was made by serologic testing, polymerase chain reaction detection, and immunohistochemical testing of the organism from a skin biopsy specimen.

Anti-Bacterial Agents↗

Rickettsia prowazekii and real-time polymerase chain reaction.

Rickettsia prowazekii is the causative agent of epidemic typhus and a potential bioterrorism agent. Sensitive and specific rapid assays are needed to complement existing methods of detecting this organism. We developed a real-time quantitative polymerase chain reaction assay by using a species-specific probe targeting the gltA gene. This assay, which was rapid, specific for R. prowazekii only, and sensitive (cutoff detection of 1 to 5 copies per sample), detected and directly identified R. prowazekii in blood of 12 experimentally infected mice sampled at day 3 and 6 postinfection or in naturally or experimentally infected lice. Because our assay is highly standardized and easily adaptable, it could improve epidemic typhus surveillance in public health programs, especially for countries with underdiagnosed or unrecognized human cases.

Animals↗

Lymph node biopsy specimens and diagnosis of cat-scratch disease.

We report microbiologic analysis of 786 lymph node biopsy specimens from patients with suspected cat-scratch disease (CSD). The specimens were examined by standard, cell culture, and molecular methods. Infectious agents were found in samples from 391 (49.7%) of 786 patients. The most commonly identified infectious agent was Bartonella henselae (245 patients, 31.2%), the agent of CSD. Mycobacteriosis was diagnosed in 54 patients (6.9%) by culture and retrospectively confirmed by using a specific real-time PCR assay. Neoplasm was diagnosed in 181 specimens suitable for histologic analysis (26.0%) from 47 patients. Moreover, 13 patients with confirmed Bartonella infections had concurrent mycobacteriosis (10 cases) or neoplasm (3 cases). A diagnosis of CSD does not eliminate a diagnosis of mycobacteriosis or neoplasm. Histologic analysis of lymph node biopsy specimens should be routinely performed because some patients might have a concurrent malignant disease or mycobacteriosis.

Adolescent↗

Scrub typhus in Himalayas.

Himachal Pradesh state of India is situated in the outer Himalayan ranges. During the rainy season, several cases of acute febrile illness of unknown origin occurred. Orientia tsutsugamushi was identified as the causative agent by microimmunofluorescence and PCR. Two new genotypes of O. tsutsugamushi were identified in the region.

Fever↗

Molecular detection of Bartonella quintana, B. Elizabethae, B. Koehlerae, B. Doshiae, B. Taylorii, and Rickettsia felis in rodent fleas collected in Kabul, Afghanistan.

The prevalences of Bartonella spp. and Rickettsia spp. were investigated using molecular methods in 77 rodent fleas collected in November 2002 by the French forces detachment in Kabul, Afghanistan. Overall, Bartonella DNA was detected in 15.5% of gerbil fleas and 40.5% of rat fleas, whereas Rickettsia felis was found in 9% of gerbil fleas. We described for the first time in this country Bartonella quintana, B. koehlerae, B. taylorii, and Rickettsia felis in fleas from the gerbil species Meriones lybicus, and B. elizabethae and B. doshiae in rat fleas. Of these, B. quintana, B. elizabethae, B. koehlerae, and R. felis are recognized human pathogens. These results emphasize the potential risk of flea-borne infections transmitted by rodents in this area, and suggest that preventive measures should be taken in the general framework of zoonoses management.

Afghanistan↗

First molecular detection of Rickettsia felis in fleas from Algeria.

Fleas collected in Algeria in the district of Oran between July and September 2003 were tested by polymerase chain reaction for the presence of Rickettsia spp. DNA using primers amplifying gltA and OmpA genes. Two gltA sequences identical to those of an emerging pathogen, Rickettsia felis, were detected including i) R. felis California 2 in Ctenocephalides canis from rodents and ii) R. felis RF2125 in Archeopsylla erinacei from hedgehogs.

Algeria↗

Antiangiogenic effect of erythromycin: an in vitro model of Bartonella quintana infection.

BACKGROUND: Bartonella quintana, the etiological agent of bacillary angiomatosis (BA), causes endothelial cell proliferation. Erythromycin has dramatic effects on BA, and the effects are largely unexplained by the compound's bacteriostatic properties. Our aim here was to evaluate the possibility that erythromycin alters angiogenesis. METHODS: The effect of erythromycin on B. quintana-induced endothelial cell proliferation was studied using a wild-type strain and an erythromycin-resistant B. quintana mutant. The latter was generated by serial subcultures on blood agar plates. RESULTS: We show that erythromycin significantly inhibits the proliferation of dermal microvascular endothelial cells induced either by wild-type B. quintana or by our erythromycin-resistant mutant. Doxycycline and gentamycin failed to exert such an effect. Finally, we found that the resistant strain harbored a 27-bp insertion in the highly conserved region of the gene encoding the ribosomal protein L4; this insertion may explain the existence of the resistance to erythromycin. CONCLUSION: The data presented here indicate that erythromycin profoundly down-modulates endothelial cell proliferation irrespective of its bacteriostatic effects and suggest that this may be a key component of the efficacy of the compound in the treatment of patients with BA.

Amino Acid Sequence↗

Prevalence of human pathogens in cat and dog fleas in New Zealand.

AIMS: To provide further information on the prevalence of Rickettsia felis, Bartonella hensela, and B. clarridgeiae in cat and dog fleas in New Zealand and their distribution in the country. METHODS: We used PCR and sequencing with primers for the its and pap 31 (for Bartonella spp.), and the gltA and OmpB (for Rickettsia spp.) genes on DNA from fleas collected from dogs and cats presenting to 3 widely separated veterinary practices on the North Island. RESULTS: DNA of R. felis (19%), B. henselae (11%), and B. clarridgeiae (7%) was found in the 114 cat fleas (Ctenocephalides felis) we studied. The DNA of both B. henselae and B. clarridgeiae was found in 3 fleas (from 2 animals); B. clarridgeiae and R. felis in 1 flea; B. henselae and R. felis in 5 fleas (from 3 animals); and R. felis, B. henselae, and B. clarridgeiae in 2 fleas (from 1 animal). No amplicons were obtained from 3 dog fleas (Ctenocephalides canis). CONCLUSIONS: The emerging human pathogens, R. felis, B. henselae, and B. clarridgeiae, are prevalent and widely distributed in cat fleas in the North Island of New Zealand.

Animals↗

[Propionibacterium acnes adenitis].

INTRODUCTION: Propionibacterium acnes is a gram-positive pleomorphic rod-shaped anaerobic saprophyte of the skin, mouth and upper respiratory tract. Although associated with acne vulgaris, it is otherwise reported as a human pathogen only rarely, in various infections, notably cutaneous and osteoarticular, and in endocarditis. We report here a case of bilateral P. acnes-abscessed adenitis of the inguinal folds. CASE: A 32 year-old man presented with inguinal lymph nodes that had progressively and bilaterally reddened and become painful, with fistulation of the skin and pus. Culture of a surgical sample identified P. acnes. DISCUSSION: Although this strain has been associated with lymph node granuloma, especially in sarcoidosis, abscessed lymph node infection as seen in our patient has never been reported.

Adult↗