Mycoplasma penetrans bacteremia in an immunocompromised patient detected by metagenomic sequencing: a case report.

BACKGROUND: Mycoplasma sp. are well recognized as etiological agents of respiratory and sexually transmitted disease. Mycoplasma penetrans, a species of Mycoplasma sp., has been frequently detected in HIV-positive patients and associated with the progression of HIV-associated disease. To date, there is only a single case report describing M. penetrans as the causative agent of a severe respiratory tract infection in a HIV-negative patient. CASE PRESENTATION: In this report, we describe the case of M. penetrans bacteremia in a HIV-negative, 38-year-old, female, immunocompromised, solid organ transplant patient (combined kidney and pancreas transplantation in 2016), who was admitted to our hospital with anemic uterine bleeding and fever of 38.3 °C. Several hours before her admission at our university hospital, a latex bladder catheter was inserted into her uterus and she complained about fatigue, dizziness and ongoing vaginal bleeding. Laboratory examination showed severe anemia, but microbiological examination was inconspicuous (culture negative vaginal and cervical smears, negative urine culture). Bacterial blood cultures showed a growth signal after 4 h, but microscopic examination with Gram staining and subcultures on different agar media did not identify bacterial pathogens. To identify the bacterial cause of malignancy in the patient, metagenomic sequencing of the blood culture was performed that identified M. penetrans. CONCLUSION: Metagenomic sequencing identified M. penetrans in an immunosuppressed patient with culture-negative bacteremia. Clinicians should be aware of the opportunistic potential of M. penetrans that may cause severe infections in certain vulnerable patient populations and the limitations of culture and Gram staining for confirming the presence of fastidious bacterial pathogens like Mycoplasma spp.

Transmission of a common intestinal neoplasm in zebrafish by cohabitation.

Intestinal neoplasms are common in zebrafish (Danio rerio) research facilities. These tumours are most often seen in older fish and are classified as small cell carcinomas or adenocarcinomas. Affected fish populations always contain subpopulations with preneoplastic lesions, characterized by epithelial hyperplasia or inflammation. Previous observations indicated that these tumours are unlikely caused by diet, water quality or genetic background, suggesting an infectious aetiology. We performed five transmission experiments by exposure of naïve fish to affected donor fish by cohabitation or exposure to tank effluent water. Intestinal lesions were observed in recipient fish in all exposure groups, including transmissions from previous recipient fish, and moribund fish exhibited a higher prevalence of neoplasms. We found a single 16S rRNA sequence, most similar to Mycoplasma penetrans, to be highly enriched in the donors and exposed recipients compared to unexposed control fish. We further tracked the presence of the Mycoplasma sp. using a targeted PCR test on individual dissected intestines or faeces or tank faeces. Original donor and exposed fish populations were positive for Mycoplasma, while corresponding unexposed control fish were negative. This study indicates an infectious aetiology for these transmissible tumours of zebrafish and suggests a possible candidate agent of a Mycoplasma species.

Epidemiology of Mycoplasma acquisition in male HIV-1 infected patients: a multistage cross-sectional survey in Jiangsu, China.

Mycoplasma infections are most frequently associated with disease in the urogenital or respiratory tracts and, in most cases, mycoplasmas infect the host persistently. In HIV-infected individuals the prevalence and role of genital mycoplasmas has not been well studied. To investigate the six species of Mycoplasma and the risk factors for infection in Jiangsu province, first-void urine and venous blood samples were collected and epidemiological questionnaires were administered after informed consent. A total of 1541 HIV/AIDS patients were recruited in this study. The overall infection rates of six Mycoplasma species were: Ureaplasma urealyticum (26·7%), Mycoplasma hominis (25·3%), M. fermentans (5·1%), M. genitalium (20·1%), M. penetrans (1·6%) and M. pirum (15·4%). The Mycoplasma infection rate in the unmarried group was lower than that of the married, divorced and widowed groups [adjusted odds ratio (aOR) 1·432, 95% confidence interval (CI) 1·077-1·904, P < 0·05]. The patients who refused highly active antiretroviral therapy (HAART) had a much higher risk of Mucoplasma infection (aOR 1·357, 95% CI 1·097-1·679, P < 0·05). Otherwise, a high CD4+ T cell count was a protective factor against Mycoplasma infection (aOR 0·576, 95% CI 0·460-0·719, P < 0·05). Further research will be required to confirm a causal relationship and to identify risk factors for Mycoplasma infection in HIV/AIDS populations.

[Isolation of Mycoplasma penetrans and detection of the levels of serum IL-6 and TNF-alpha in the blood of patients with autoimmune disease].

AIM: To investigate the isolation of Mycoplasma penetrans from the blood of autoimmune disease patients and to evaluate the levels of serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in patients with autoimmune disease (AID). METHODS: M. penetrans was isolated and cultured from the blood specimens of 44 patients with AID. Among them 16 patients were control group I, who were the objects. 28 patients were in control group II as contrast. The serum ASO or RF level of the patients in control group I was higher than that in control group II. The positive specimens were confirmed by nPCR and the levels of IL-6 and TNF-alpha were measured by RIA in the blood samples. RESULTS: M. penetrans was detected in the blood of 17 patients and the positive detection rate was 38.6% (17/44) in AID group. There was significant difference between the detection rate from group I (12.5%, 2/16, P<0.01) and that in group II (0%, 0/28, P<0.01). The serum level of IL-6 in the AID with M. penetrans infection patients in group I (3.30+/-1.49) microg/L was significantly different from that in the AID without M. penetrans infection patients in group I (2.43+/-0.95) microg/L and that in group II(1.14+/-0.32) microg/L, P<0.01. The serum level of TNF-alpha in the AID with M. penetrans infection patients in group I (293.3+/-179.9) ng/L was significantly different from that in the AID without M. penetrans infection patients in group I (173.9+/-73.9) ng/L and that in group II(108.8+/-33.8) ng/L, P<0.01. CONCLUSION: M. penetrans occurs with high frequency in the blood of autoimmune disease patients. The evident increase of serum levels of IL-6 and TNF-alpha in AID with M. penetrans infection than the control groups.

Mycoplasma penetrans infections and seroconversion in patients with AIDS: identification of major mycoplasmal antigens targeted by host antibody response.

We examined Mycoplasma penetrans-specific antibodies in sera of five male homosexual AIDS patients from whom M. penetrans was isolated during the disease process. No consistent immune reaction pattern could be recognized in Western blot using whole cell proteins. Serum samples obtained prior to M. penetrans isolation reacted with a number of M. penetrans proteins, most likely due to non-specific cross-reactions. Further analysis revealed that patients produced prominent antibody reaction to lipid-associated membrane proteins (LAMPs) of M. penetrans at the time of mycoplasma isolation, which could not be observed for serum samples obtained prior to M. penetrans isolation. The positive antibody reaction was mainly directed against two major LAMPs of M. penetrans with molecular mass of 35 and 38 kDa and produced a distinctive pattern of positive immunoreaction bands. Our observation suggested that, comparing with whole mycoplasmal proteins, LAMPs were more specific target antigens in serological assays for M. penetrans infection.

Seroprevalencia de Mycoplasma ssp. en mujeres con esterilidad / Serological prevalence of Mycoplasma ssp. in infertile women

Objetivo: Investigar la prevalencia serológica de Mycoplasmas genitalium, M. fermentans y M. penetrans en mujeres con esterilidad, y compararla con la de mujeres fértiles. Material y métodos: Estudiamos a 55 mujeres estériles por factor tuboperitoneal y a 55 mujeres clínicamente fértiles, evaluando la prevalencia serológica dentro de cada grupo y comparándolas. Resultados: La prevalencia, comparando grupo estéril y fértil fue, respectivamente: IgM: M. genitalium (27,27 y 30,91%; p = 0,152), M. fermentans (83,64 y 61,82%; p = 0,006), M. penetrans (38,18 y 49,09%; p = 0,079); IgA: M. genitalium (5,45 y 1,82%; p = 0,250), M. fermentans (0,00 y 12,73%; p = 0,006), M. penetrans (36,36 y 3,64%; p < 0,001), e IgG: M. genitalium (92,73 y 92,73%; p = 0,284), M. fermentans (65,45 y 40,00%; p = 0,004), M. penetrans (96,36 y 9,09%; p < 0,001). Conclusión: Para M. genitalium no hubo diferencia estadística entre ambos grupos. Las IgG están significativamente más elevadas en el grupo estéril que en el grupo fértil para M. fermentans y M. penetrans, lo que los relaciona con una mayor probabilidad etiológica o factores de riesgo de enfermedad inflamatoria pelviana y consecuentemente a esterilidad

Objectives: To investigate the serological prevalence of Mycoplasmas genitalium, M. fermentans and M. penetrans in infertile women compared with fertile women. Material and methods: We studied 55 women with infertility due to peritoneal-tubal factors and 55 fertile women. The serological prevalence in each group was evaluated and the results were compared. Results: The prevalence of IgM in the infertile and fertile groups was, respectively: M. genitalium (27.27% vs 30.91%; p = 0.152), M. fermentans (83.64% vs 61.82%; p = 0.006), M. penetrans (38.18% vs 49.09%; p = 0.079). IgA: M. genitalium (5.45% vs 1.82%; p = 0.250), M. fermentans (0.00% vs 12.73%; p = 0.006), M. penetrans (36.36% vs 3.64%; p < 0.001). IgG: M. genitalium (92.73% vs 92.73%; p = 0.284), M. fermentans (65.45% vs 40.00%; p = 0.004), M. penetrans (96.36% vs 9.09%; p < 0.001). Conclusions: No statistically significant differences were found in the prevalence of M. genitalium between the infertile and the fertile groups. IgG for M. fermentans and M. penetrans were significantly higher in the infertile group than in the fertile group, suggesting that these microorganisms could be the cause of, or risk factors for, pelvic inflammatory disease and female infertility

Phase variation among major surface antigens of Mycoplasma penetrans.

The pathogenicity and prevalence of Mycoplasma penetrans, a Mycoplasma species recently isolated from humans, are still debated. A major P35 antigen, which is used as target epitope in serological assays, was shown to be a phase-variable lipid-associated membrane protein (LAMP). In this study, we performed a comparative analysis of the LAMP patterns from five M. penetrans clinical isolates and from the type strain. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles and immunoblots with sera serially collected from an M. penetrans-infected patient indicated that these strains expressed different LAMP repertoires. Furthermore, the intraclonal variation in the expression of LAMPs (P34A, P34B, P35, and P38) was monitored by immunoblot analysis with three specific monoclonal antibodies (MAbs) developed in this study and MAb 7 to P35. The phase variation of these LAMPs occurs in an independent manner, with frequencies of variation ranging from 10(-2) to 10(-4) per cell per generation. Consistent with their amphipathic nature, the P34B and P38 antigens were found exposed at the cell surface. The DNA sequence encoding the P38 antigen was defined and found to be related to those of the P35 gene and other putative LAMP-encoding genes, suggesting that these variable antigens are encoded by a family of related genes. Finally, the serum samples from an M. penetrans-infected patient contained antibodies that reacted with a P36 antigen expressed in different M. penetrans strains but not in the isolate recovered from this patient. This result suggested that in vivo phase variation of P36 occurred, which would support a role for these LAMP variations in avoiding the host's immune vigilance.

[New type pathogenic mycoplasmas isolated from female patients with genital infection in Nanjing, China].

OBJECTIVE: To study if infection of new type pathogenic mycoplasmas, Mycoplasma penetrans (Mpe), Mycoplasma fermentans (Mf), and Mycoplasma pirum (Mpi), exists in the genital tract of gynecologic patients with genital infection in China so as to provide information for clinical diagnosis and therapy. METHODS: Cervical secretions from 172 patients with infectious diaseses of gentital tract and 172 healthy controls were collected and inoculated in improved SP-4 culture medium. Biochemical reaction, coagglutination test, metabolism-inhibition test, polymerase chain reaction (PCR) assay, and DNA sequencing were employed to identify the isolated microorganisms. RESULTS: One strain of Mycoplasma penetrans (0.58%) and two strains of Mycoplasma fermentans (1.16%) were isolated from the cervical secretions of patients, but none was found in healthy controls. CONCLUSION: Mpe infection and Mf infection exist in female patients with genital infection in Nanjing.

Mycoplasma species in rapid and slow HIV progressors.

We determined the relationship between the presence of Mycoplasma fermentans and Mycoplasma penetrans and the rate of progression of HIV-associated disease in a nested case-control study based on a cohort of 159 HIV-infected patients with different rates of disease progression. Study participants were divided into 3 progression groups: non-progressors who had been HIV-1 seropositive for at least 9 years and had remained asymptomatic with a CD4 cell count of > 500/mm3; slow progressors who had been HIV-1 seropositive for at least 9 years and whose CD4 cell count had fallen below 500 cells, and who had developed symptomatic disease or AIDS; and rapid progressors who had developed AIDS within 5 years of HIV infection. Peripheral blood mononuclear cells (PBMCs) were collected at enrollment and examined by mycoplasma polymerase chain reaction (PCR) assays. Three (7%) of 46 non-progressors, 3 (3%) of 86 slow progressors, and 2 (7%) of 27 rapid progressors were M. fermentans positive. The PBMCs from 91 subjects were tested for M. penetrans DNA and none was positive. The small proportion of M. fermentans-positive patients indicates that the mycoplasma cannot be important in the development of AIDS in the large majority of patients. Furthermore, no association was found between its presence and more rapid HIV disease progression.

Mycoplasma penetrans bacteremia and primary antiphospholipid syndrome.

Mycoplasma penetrans, a rare bacterium so far only found in HIV-infected persons, was isolated in the blood and throat of a non-HIV-infected patient with primary antiphospholipid syndrome (whose etiology and pathogenesis are unknown).

Detection of mycoplasmas in urethral swabs from HIV-1 infected patients and control individuals using culture techniques and polymerase chain reaction.

The objective of the present study was to determine the prevalence of certain mycoplasma species, i.e., Mycoplasma hominis, Ureaplasma urealyticum and Mycoplasma penetrans, in urethral swabs from HIV-1 infected patients compared to swabs from a control group. Mycoplasmas were detected by routine culture techniques and by the Polymerase Chain Reaction (PCR) technique, using 16SrRNA generic primers of conserved region and Mycoplasma penetrans specific primers. The positivity rates obtained with the two methods were comparable. Nevertheless, PCR was more sensitive, while the culture techniques allowed the quantification of the isolates. The results showed no significant difference (p < 0.05) in positivity rates between the methods used for mycoplasma detection.

Detection of mycoplasmas in urethral swabs from HIV-1 infected patients and control individuals using culture techniques and polymerase chain reaction

O objetivo do presente estudo foi determinar a prevalência de determinadas espécies de micoplasmas, tais como, Mycoplasma hominis, Ureaplasma urealyticum e Mycoplasma penetrans, em swabs uretrais de pacientes infectados com HIV-1 comparando com um grupo controle. Micoplasmas foram detectados por técnicas padräo de cultivo e pela reacäo de polimerase em cadeia para a qual foram utilizados "primers" genericos obtidos da regiäo conservada 16sRNA e "primers" nos dois metodos foi comparavel. Contudo, o PCR mostrou ser mais sensivel nas condicöes empregadas enquanto que o cultivo permitiu a quantificacäo dos isolados. Os resultados demonstraram näo haver diferenças significantes (p<0,05) nas taxas de positividade entre os metodos empregados para a detecçäo dos micoplasmas

Mycoplasma fermentans, but not M penetrans, detected by PCR assays in synovium from patients with rheumatoid arthritis and other rheumatic disorders.

AIM/BACKGROUND: Mycoplasmas, especially Mycoplasma fermentans, were suggested more than 20 years ago as a possible cause of rheumatoid arthritis but this hypothesis was never substantiated. In view of the superior sensitivity of the polymerase chain reaction (PCR) assay over culture, the aim was to use this method to seek M fermentans and M penetrans in synovial samples from patients with various arthritides. METHODS: Synovial fluid samples (n = 154) and synovial biopsy specimens (n = 20) from 133 patients with various rheumatic disorders were stored at -80 degrees C for between one and 40 months. Aliquots (500 microliters) of the synovial fluid samples were centrifuged and the deposit, and also the synovial biopsy specimens (approximately 1 g) were placed in lysis buffer with proteinase K for DNA extraction. The DNA was tested by using a semi-nested PCR assay for M fermentans and a single-round PCR for M penetrans. RESULTS: M fermentans was detected in the joints of eight (21%) of 38 patients with rheumatoid arthritis, two (20%) of 10 patients with spondyloarthropathy with peripheral arthritis, one (20%) of five patients with psoriatic arthritis, and four (13%) of 31 patients with unclassified arthritis. M fermentans was not found in the joints of the seven patients with reactive arthritis, the 29 with osteoarthritis or post-traumatic hydrarthrosis, the nine with gouty arthritis, nor the four with chronic juvenile arthritis. M penetrans was not detected in any sample. CONCLUSIONS: These findings show that the presence of M fermentans in the joint is associated with inflammatory rheumatic disorders of unknown cause, including rheumatoid arthritis. However, whether this organism triggers or perpetuates disease of behaves as a passenger remains conjectural.

Failure to detect Mycoplasma fermentans, Mycoplasma penetrans, or Mycoplasma pirum in the urethra of patients with acute nongonococcal urethritis.

Urethral swab specimens collected from 108 male Japanese patients with acute nongonococcal urethritis (NGU) and from 50 Japanese men without NGU were examined for the presence of Mycoplasma fermentans, Mycoplasma penetrans, and Mycoplasma pirum by means of polymerase chain reaction-based assays. These mycoplasmas were not detected in any of the specimens, which suggests that they are unlikely to have a pathogenic role in acute NGU.

Association of Mycoplasma penetrans with human immunodeficiency virus infection.

A cross-sectional study was done to determine the seroprevalence of Mycoplasma penetrans in human immunodeficiency virus (HIV) type 1-seropositive and -seronegative persons recruited in France. The data were analyzed with respect to the sociodemographic, clinical, and biologic status of the patients. M. penetrans seropositivity was associated with HIV infection (18.2% of HIV-seropositive vs. 1.3% of HIV-seronegative persons were M. penetrans-seropositive; P < .001). M. penetrans infection was predominantly but not exclusively associated with homosexual practices in HIV-seropositive subjects and thus presumably sexually transmitted. M. penetrans seroprevalence increased with progression of HIV-associated disease. No association was found between M. penetrans and Kaposi's sarcoma. Thus, there is an unambiguous association between M. penetrans and HIV, particularly among homosexual persons, but its clinical significance remains to be investigated.