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Trichomonas vaginalis and Mycoplasma hominis: new tales of two old friends

  • Daniele Dessì (a1) (a2), Valentina Margarita (a1), Anna Rita Cocco (a1), Alessandra Marongiu (a1), Pier Luigi Fiori (a1) and Paola Rappelli (a1)...


Trichomonas vaginalis is an anaerobic protist, responsible for the most prevalent non-viral sexually transmitted infection in humans. One of the most intriguing aspects of T. vaginalis pathobiology is the complex relationship with intracellular microbial symbionts: a group of dsRNA viruses belonging to family of Totiviridae (T. vaginalis virus), and eubacteria belonging to the Mycoplasma genus, in particular Mycoplasma hominis. Both microorganisms seem to strongly influence the lifestyle of T. vaginalis, suggesting a role of the symbiosis in the high variability of clinical presentation and sequelae during trichomoniasis. In the last few years many aspects of this unique symbiotic relationship have been investigated: M. hominis resides and replicates in the protozoan cell, and T. vaginalis is able to pass the bacterial infection to both mycoplasma-free protozoan isolates and human epithelial cells; M. hominis synergistically upregulates the proinflammatory response of human monocytes to T. vaginalis. Furthermore, the influence of M. hominis over T. vaginalis metabolism and physiology has been characterized. The identification of a novel species belonging to the class of Mollicutes (Candidatus Mycoplasma girerdii) exclusively associated to T. vaginalis opens new perspectives in the research of the complex series of events taking place in the multifaceted world of the vaginal microbiota, both under normal and pathological conditions.


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Author for correspondence: Pier Luigi Fiori, E-mail:


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Allen-Daniels, MJ, Serrano, MG, Pflugner, LP, Fettweis, JM, Prestosa, MA, Koparde, VN, Brooks, JP, Strauss, JF, Romero, R, Chaiworapongsa, T, Eschenbach, DA, Buck, GA and Jefferson, KK (2015) Identification of a gene in Mycoplasma hominis associated with preterm birth and microbial burden in intraamniotic infection. American Journal of Obstetrics and Gynecology 212, 779. e1-779.e13.
Bär, A-K, Phukan, N, Pinheiro, J and Simoes-Barbosa, A (2015) The interplay of host microbiota and parasitic protozoans at mucosal interfaces: implications for the outcomes of infections and diseases. PLOS Neglected Tropical Diseases 9, e0004176.
Barykova, YA, Logunov, DY, Shmarov, MM, Vinarov, AZ, Fiev, DN, Vinarova, NA, Rakovskaya, IV, Baker, PS, Shyshynova, I, Stephenson, AJ, Klein, EA, Naroditsky, BS, Gintsburg, AL and Gudkov, AV (2011) Association of Mycoplasma hominis infection with prostate cancer. Oncotarget 2, 289297.
Bronte, V and Zanovello, P (2005) Regulation of immune responses by L-arginine metabolism. Nature Reviews Immunology 5, 641654.
Butler, SE, Augostini, P and Secor, WE (2010) Mycoplasma hominis infection of Trichomonas vaginalis is not associated with metronidazole-resistant trichomoniasis in clinical isolates from the United States. Parasitology Research 107, 10231027.
Costello, EK, Sun, CL, Carlisle, EM, Morowitz, MJ, Banfield, JF and Relman, DA (2017) Candidatus Mycoplasma girerdii replicates, diversifies, and co-occurs with Trichomonas vaginalis in the oral cavity of a premature infant. Scientific Reports 7, 111.
da Luz Becker, D, dos Santos, O, Frasson, AP, de Vargas Rigo, G, Macedo, AJ and Tasca, T (2015) High rates of double-stranded RNA viruses and Mycoplasma hominis in Trichomonas vaginalis clinical isolates in South Brazil. Infection, Genetics and Evolution 34, 181187.
Dessì, D, Delogu, G, Emonte, E, Catania, MR, Fiori, PL and Rappelli, P (2005) Long-term survival and intracellular replication of Mycoplasma hominis in Trichomonas vaginalis cells: potential role of the protozoon in transmitting bacterial infection. Infection and Immunity 73, 11801186.
Diaz, N, Dessì, D, Dessole, S, Fiori, PL and Rappelli, P (2010) Rapid detection of coinfections by Trichomonas vaginalis, Mycoplasma hominis, and Ureaplasma urealyticum by a new multiplex polymerase chain reaction. Diagnostic Microbiology and Infectious Disease 67, 3036.
Edwards, T, Burke, P, Smalley, H and Hobbs, G (2014) Trichomonas vaginalis: clinical relevance, pathogenicity and diagnosis. Critical Reviews in Microbiology 18, 112. doi: 10.3109/1040841X.2014.958050.
Fettweis, JM, Serrano, MG, Huang, B, Brooks, JP, Glascock, AL, Sheth, NU, Strauss, JF, Jefferson, KK and Buck, GA (2014) An emerging mycoplasma associated with trichomoniasis, vaginal infection and disease. PLoS ONE 9, e110943.
Fichorova, RN (2009) Impact of T. vaginalis infection on innate immune responses and reproductive outcome. Journal of Reproductive Immunology 83, 185189.
Fichorova, RN, Lee, Y, Yamamoto, HS, Takagi, Y, Hayes, GR, Goodman, RP, Chepa-Lotrea, X, Buck, OR, Murray, R, Kula, T, Beach, DH, Singh, BN and Nibert, ML (2012) Endobiont viruses sensed by the human Host – beyond conventional antiparasitic therapy. PLoS ONE 7, e48418.
Fichorova, R, Fraga, J, Rappelli, P and Fiori, PL (2017) Trichomonas vaginalis infection in symbiosis with Trichomonas virus and Mycoplasma. Research in Microbiology 168, 882891.
Figueroa-Angulo, EE, Rendón-Gandarilla, FJ, Puente-Rivera, J, Calla-Choque, JS, Cárdenas-Guerra, RE, Ortega-López, J, Quintas-Granados, LI, Alvarez-Sánchez, ME and Arroyo, R (2012) The effects of environmental factors on the virulence of Trichomonas vaginalis. Microbes and Infection 14, 14111427.
Fiori, PL, Rappelli, P and Addis, MF (1999) The flagellated parasite Trichomonas vaginalis: new insights into cytopathogenicity mechanisms. Microbes and Infection 1, 149156.
Fiori, PL, Diaz, N, Cocco, AR, Rappelli, P and Dessì, D (2013) Association of Trichomonas vaginalis with its symbiont Mycoplasma hominis synergistically upregulates the in vitro proinflammatory response of human monocytes. Sexually Transmitted Infections 89, 449454.
Fraga, J, Rodríguez, N, Fernández, C, Mondeja, B, Sariego, I, Fernández-Calienes, A and Rojas, L (2012) Mycoplasma hominis in Cuban Trichomonas vaginalis isolates: association with parasite genetic polymorphism. Experimental Parasitology 131, 393398.
Fulde, M, Willenborg, J, de Greeff, A, Benga, L, Smith, HE, Valentin-Weigand, P and Goethe, R (2011) Argr is an essential local transcriptional regulator of the arcABC operon in Streptococcus suis and is crucial for biological fitness in an acidic environment. Microbiology (Reading, England) 157, 572582.
Fürnkranz, U, Henrich, B and Walochnik, J (2018) Mycoplasma hominis impacts gene expression in Trichomonas vaginalis. Parasitology Research 117, 841847.
Gagnaire, A, Nadel, B, Raoult, D, Neefjes, J and Gorvel, JP (2017) Collateral damage: insights into bacterial mechanisms that predispose host cells to cancer. Nature Reviews Microbiology 15, 120.
Goret, J, Béven, L, Faustin, B, Contin-bordes, C, Le Roy, C, Claverol, S, Renaudin, H, Bebear, C and Pereyre, S (2017) Interaction of Mycoplasma hominis PG21 with human dendritic cells: interleukin- 23-inducing mycoplasmal lipoproteins and inflammasome activation of the cell. Journal of Bacteriology 199, 115.
Hampl, V, Vaňáčová, Š, Kulda, J and Flegr, J (2001) Concordance between genetic relatedness and phenotypic similarities of Trichomonas vaginalis strains. BMC Evolutionary Biology 1, 11.
Hasebe, A, Mu, H and Cole, BC (2014) A potential pathogenic factor from Mycoplasma hominis is a TLR2-dependent, macrophage-activating, P50-related adhesin. American Journal of Reproductive Immunology 72, 285295.
Henrich, B, Kretzmer, F, Deenen, R and Köhrer, K (2017) Validation of a novel Mho microarray for a comprehensive characterisation of the Mycoplasma hominis action in HeLa cell infection. PLoS ONE 12, 120.
Hirt, RP and Sherrard, J (2015) Trichomonas vaginalis origins, molecular pathobiology and clinical considerations. Current Opinion in Infectious Diseases 28, 7279.
Hopfe, M, Deenen, R, Degrandi, D, Köhrer, K and Henrich, B (2013) Host cell responses to persistent Mycoplasmas – different stages in infection of HeLa cells with Mycoplasma hominis. PLoS ONE 8, e54219.
Huang, K-Y, Chen, Y-YM, Fang, Y-K, Cheng, W-H, Cheng, C-C, Chen, Y-C, Wu, TE, Ku, F-M, Chen, S-C, Lin, R and Tang, P (2014) Adaptive responses to glucose restriction enhance cell survival, antioxidant capability, and autophagy of the protozoan parasite Trichomonas vaginalis. Biochimica et Biophysica Acta (BBA) – General Subjects 1840, 5364.
Jules, M and Buchrieser, C (2007) Legionella pneumophila adaptation to intracellular life and the host response: clues from genomics and transcriptomics. FEBS Letters 581, 28292838.
Kissinger, P (2015) Trichomonas vaginalis: a review of epidemiologic, clinical and treatment issues. BMC Infectious Diseases 15, 307.
Klebanoff, MA, Carey, JC, Hauth, JC, Hillier, SL, Nugent, RP, Thom, EA, Ernest, JM, Heine, RP, Wapner, RJ, Trout, W, Moawad, A, Miodovnik, M, Sibai, BM, Van Dorsten, JP, Dombrowski, MP, O'Sullivan, MJ, Varner, M, Langer, O, McNellis, D, Roberts, JM and Leveno, KJ (2001) Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection. New England Journal of Medicine 345, 487493.
Linstead, D and Cranshaw, MA (1983) The pathway of arginine catabolism in the parasitic flagellate Trichomonas vaginalis. Molecular and Biochemical Parasitology 8, 241252.
Margarita, V, Rappelli, P, Dessì, D, Pintus, G, Hirt, RP and Fiori, PL (2016) Symbiotic association with Mycoplasma hominis can influence growth rate, ATP production, cytolysis and inflammatory response of Trichomonas vaginalis. Frontiers in Microbiology 7, 953.
McClelland, RS, Sangare, L, Hassan, WM, Lavreys, L, Mandaliya, K, Kiarie, J, Ndinya-Achola, J, Jaoko, W and Baeten, JM (2007) Infection with Trichomonas vaginalis increases the risk of HIV-1 acquisition. The Journal of Infectious Diseases 195, 698702.
Mercer, F and Johnson, PJ (2018) Trichomonas vaginalis: pathogenesis, symbiont interactions, and host cell immune responses. Trends in Parasitology 34, 683693.
Mercer, F, Gerald, F, Diala, I, Chen, Y-P, Molgora, BM, Ng, SH and Johnson, PJ (2016) Leukocyte Lysis and cytokine induction by the human sexually transmitted parasite Trichomonas vaginalis. PLoS Neglected Tropical Diseases 10, e0004913.
Mercer, F, Ng, SH, Brown, TM, Boatman, G and Johnson, PJ (2018) Neutrophils kill the parasite Trichomonas vaginalis using trogocytosis. PLoS Biology 16, e2003885.
Miyahira, YTT (1991) Application of ATP measurement to evaluation of the growth of parasitic protozoa in vitro with a special reference to Pneumocystis carinii. Comparative Biochemistry and Physiology A Comparative Physiology 100, 10311034.
Morada, M, Manzur, M, Lam, B, Tan, C, Tachezy, J, Rappelli, P, Dessì, D, Fiori, PL and Yarlett, N (2010) Arginine metabolism in Trichomonas vaginalis infected with Mycoplasma hominis. Microbiology (Reading, England) 156, 37343743.
Namiki, K, Goodison, S, Porvasnik, S, Allan, RW, Iczkowski, KA, Urbanek, C, Reyes, L, Sakamoto, N and Rosser, CJ (2009) Persistent exposure to mycoplasma induces malignant transformation of human prostate cells. PLoS ONE 4, e6872.
Noh, EJ, Kang, SW, Shin, YJ, Kim, DC, Park, IS, Kim, MY, Chun, BG and Min, BH (2002) Characterization of mycoplasma arginine deiminase expressed in E. coli and its inhibitory regulation of nitric oxide synthesis. Molecules and Cells 13, 137143.
Nowack, ECM and Melkonian, M (2010) Endosymbiotic associations within protists. Philosophical Transactions of the Royal Society B: Biological Sciences 365, 699712.
Pararas, MV, Skevaki, CL and Kafetzis, DA (2006) Preterm birth due to maternal infection: causative pathogens and modes of prevention. European Journal of Clinical Microbiology and Infectious Diseases 25, 562569.
Peltier, MR, Freeman, AJ, Mu, HH and Cole, BC (2005) Characterization and partial purification of a macrophage-stimulating factor from Mycoplasma hominis. American Journal of Reproductive Immunology 54, 342351.
Pereyre, S, Sirand-Pugnet, P, Beven, L, Charron, A, Renaudin, H, Barré, A, Avenaud, P, Jacob, D, Couloux, A, Barbe, V, De Daruvar, A, Blanchard, A and Bébéar, C (2009) Life on arginine for Mycoplasma hominis: clues from its minimal genome and comparison with other human urogenital mycoplasmas. PLoS Genetics 5, e1000677.
Petrin, D, Delgaty, K, Bhatt, R and Garber, G (1998) Clinical and microbiological aspects of Trichomonas vaginalis. Clinical Microbiology Reviews 11, 300317.
Rappelli, P, Addis, MF, Carta, F and Fiori, PL (1998) Mycoplasma hominis parasitism of Trichomonas vaginalis. Lancet 352, 1286.
Rappelli, P, Carta, F, Delogu, G, Addis, MF, Dessì, D, Cappuccinelli, P and Fiori, PL (2001) Mycoplasma hominis and Trichomonas vaginalis symbiosis: multiplicity of infection and transmissibility of M. hominis to human cells. Archives of Microbiology 175, 7074.
Razin, S, Yogev, D and Naot, Y (1998) Molecular biology and pathogenicity of mycoplasmas. Microbiology and Molecular Biology Reviews 62, 10941156.
Ryan, CM, de Miguel, N and Johnson, PJ (2011) Trichomonas vaginalis: current understanding of host-parasite interactions. Essays in Biochemistry 51, 161175.
Shah, P and Swiatlo, E (2008) A multifaceted role for polyamines in bacterial pathogens. Molecular Microbiology 68, 416.
Shaio, MF, Lin, PR, Liu, JY and Yang, KD (1995) Generation of interleukin-8 from human monocytes in response to Trichomonas vaginalis stimulation. Infection and Immunity 63, 38643870.
Simhan, HN, Anderson, BL, Krohn, MA, Heine, RP, de Tejada, BM, Landers, DV and Hillier, SL (2007) Host immune consequences of asymptomatic Trichomonas vaginalis infection in pregnancy. American Journal of Obstetrics and Gynecology 196, 59. e1-59.e5.
Stark, JR, Judson, G, Alderete, JF, Mundodi, V, Kucknoor, AS, Giovannucci, EL, Platz, EA, Sutcliffe, S, Fall, K, Kurth, T, Ma, J, Stampfer, MJ and Mucci, LA (2009) Prospective study of Trichomonas vaginalis infection and prostate cancer incidence and mortality: physicians’ health study. Journal of the National Cancer Institute 101, 14061411.
Starlets, D, Gore, Y, Binsky, I, Haran, M, Harpaz, N, Shvidel, L, Becker-Herman, S, Berrebi, A and Shachar, I (2006) Cell-surface CD74 initiates a signaling cascade leading to cell proliferation and survival. Blood 107, 48074816.
Sutcliffe, S (2006) Plasma antibodies against Trichomonas vaginalis and subsequent risk of prostate cancer. Cancer Epidemiology Biomarkers & Prevention 15, 939945.
Sutcliffe, S, Giovannucci, E, Alderete, JF, Chang, T-H, Gaydos, CA, Zenilman, JM, De Marzo, AM, Willett, WC and Platz, EA (2006) Plasma antibodies against Trichomonas vaginalis and subsequent risk of prostate cancer. Cancer Epidemiology, Biomarkers & Prevention 15, 939945.
Sutcliffe, S, Neace, C, Magnuson, NS, Reeves, R and Alderete, JF (2012) Trichomonosis, a common curable STI, and prostate carcinogenesis – a proposed molecular mechanism. PLoS Pathogens 8, e1002801.
Tao, L, Han, L, Li, X, Gao, Q, Pan, L, Wu, L, Luo, Y, Wang, W, Zheng, Z and Guo, X (2014) Prevalence and risk factors for cervical neoplasia: a cervical cancer screening program in Beijing. BMC Public Health 14, 1185.
Thi Trung Thu, T, Margarita, V, Cocco, AR, Marongiu, A, Dessì, D, Rappelli, P and Fiori, PL (2018) Trichomonas vaginalis transports virulent Mycoplasma hominis and transmits the infection to human cells after metronidazole treatment: a potential role in bacterial invasion of fetal membranes and amniotic fluid. Journal of Pregnancy 2018, 16.
Thurman, AR and Doncel, GF (2011) Innate immunity and inflammatory response to Trichomonas vaginalis and bacterial vaginosis: relationship to HIV acquisition. American Journal of Reproductive Immunology (New York, NY: 1989) 65, 8998.
Truchetet, ME, Beven, L, Renaudin, H, Douchet, I, Ferandon, C, Charron, A, Blanco, P, Schaeverbeke, T, Contin-Bordes, C and Bebear, C (2011) Potential role of Mycoplasma hominis in interleukin (IL)-17-producing CD4+ T-cell generation via induction of IL-23 secretion by human dendritic cells. The Journal of Infectious Diseases 204, 17961805.
Twu, O, Dessí, D, Vu, A, Mercer, F, Stevens, GC, De Miguel, N, Rappelli, P, Cocco, AR, Clubb, RT, Fiori, PL and Johnson, PJ (2014) Trichomonas vaginalis homolog of macrophage migration inhibitory factor induces prostate cell growth, invasiveness, and inflammatory responses. Proceedings of the National Academy of Sciences of the United States of America 111, 81798184.
Van Der Schee, C, Sluiters, HJF, Van Der Meijden, WI, Van Beek, P, Peerbooms, P, Verbrugh, H and Van Belkum, A (2001) Host and pathogen interaction during vaginal infection by Trichomonas vaginalis and Mycoplasma hominis or Ureaplasma urealyticum. Journal of Microbiological Methods 45, 6167.
Vancini, RG and Benchimol, M (2008) Entry and intracellular location of Mycoplasma hominis in Trichomonas vaginalis. Archives of Microbiology 189, 718.
Vancini, RG, Pereira-Neves, A, Borojevic, R and Benchimol, M (2008) Trichomonas vaginalis harboring Mycoplasma hominis increases cytopathogenicity in vitro. European Journal of Clinical Microbiology & Infectious Diseases 27, 259267.
Wen, A, Srinivasan, U, Goldberg, D, Owen, J, Marrs, CF, Misra, D, Wing, DA, Ponnaluri, S, Miles-Jay, A, Bucholz, B, Abbas, K and Foxman, B (2014) Selected vaginal bacteria and risk of preterm birth: an ecological perspective. Journal of Infectious Diseases 209, 10871094.
World Health Organization (2012) WHO | Global incidence and prevalence of selected curable sexually transmitted infections – 2008. World Health Organization.
Xiao, JC, Xie, LF, Fang, SL, Gao, MY, Zhu, Y, Song, LY, Zhong, HM and Lun, ZR (2006) Symbiosis of Mycoplasma hominis in Trichomonas vaginalis may link metronidazole resistance in vitro. Parasitology Research 100, 123130.
Yap, EH, Ho, TH, Chan, YC, Thong, TW, Ng, GC, Ho, LC and Singh, M (1995) Serum antibodies to Trichomonas vaginalis in invasive cervical cancer patients. Genitourinary Medicine 71, 402404.
Yarlett, N, Martinez, MP, Ali Moharrami, M and Tachezy, J (1996) The contribution of the arginine dihydrolase pathway to energy metabolism by Trichomonas vaginalis. Molecular and Biochemical Parasitology 78, 117125.
Zakariah, M, Khan, S, Chaudhary, AA, Rolfo, C, Ben Ismail, MM and Alotaibi, YA (2018) To decipher the Mycoplasma hominis proteins targeting into the endoplasmic reticulum and their implications in prostate cancer etiology using next-generation sequencing data. Molecules 23, 112.
Zuo, X, Lockwood, BC and Coombs, GH (1995) Uptake of amino acids by the parasitic, flagellated protist Trichomonas vaginalis. Microbiology (Reading, England) 141, 26372642.



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