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Korean Journal of Pediatrics

<i>Ureaplasma urealyticum</i>or<i>Ureaplasma parvum</i>: what's the difference?

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474 http://dx.doi.org/10.3345/kjp.2013.56.5.202Ureaplasma urealyticum or Ureaplasma parvum: what’s the difference? Tae-Jung Sung, MDDepartment of Pediatrics, Hallym University Kangnam Sacred Heart Hospital, Seoul, KoreaCorresponding author: Tae-Jung Sung, MDDepartment of Pediatrics, Hallym University Kangnam Sacred Heart Hospital, 1 Singil-ro, Yeongdeungpo-gu, Seoul 150-950, Korea Tel: +82-2-829-5148Fax: +82-2-829-4469E-mail: neosung@hallym.or.kr Received: 27 August, 2013Accepted: 9 October, 2013Copyright © 2013 by The Korean Pediatric SocietyThis is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.EditorialKorean J Pediatr 2013;56(11):474-476http://dx.doi.org/10.3345/kjp.2013.56.11.474pISSN 1738-1061•eISSN 2092-7258 Korean J PediatrRecently, birth of premature babies and low birth weight babies has been increasing and survival rate of very low birth weight babies even under 500 g not to mention under 1,000 g is remarkably enhanced thanks to the development of neonatology. With the enhanced birth rate and survival rate, the issue of pediatrics majoring in neonatology is not increasing survival rate anymore but making them healthier babies. While treating premature babies in the field, it is found that some premature babies have better prognoses while others have poor prognoses.As a part of efforts to identify the factors influencing prognoses of newborns, studies on prenatal infections are actively made. One of the hottest topics is Ureaplasma infection. Although it has been studied before, it has been perceived as ‘sexually-transmitted disease’ and has been studied in gynecology or urology. Recently, however, it is expanded to the field of complications of premature babies1,2). Additionally, studies have been actively performed since strain known as Ureaplamsa urealyticum was segmented to Ureaplasma parvum (UPA hereunder) and Ureaplasma urealyticum (UUR hereunder), which were further segmented to 14 serovars2,3). Past studies published before in Korea by Lim et al.4) and by Chang et al.5) were studies on overall prevalence before Ureaplasma colonization was segmented into two serovars. In this point, Eun et al.6) is encouraging because it studied serovars of Korean premature babies. However, it has limitations at the same time. Although it is meaningful that it tried to analyze premature babies according to serovar, it dealt with UUR only and the conclusion that there would be no difference between Ureaplasma serovars may be misleading. As authors mentioned before, Ureaplasma spp is segmented to two biovars such as UPA and UUR. Such two biovars can be segmented according to genome size, 16S rRNA gene sequences, the 16S-23S rRNA intergenic region, enzyme polymorphisms, DNA-DNA hybridization, differential growth responses to manganese, and differences in the multiple banded antigen (mba) genes2,3). They are segmented to 14 serovars by polymerase chain reaction (PCR)-based methods based on the previously mentioned UPA (biovar 1, serovar 3, ATCC* 27815, NCTC** 11736), and UUA (biovar 2, serovar 8, ATCC* 27618, NCTC** 10177). According to characteristics of each serovar, serovar 1, 3, 6, and 14 fall under biovar 1, so to speak UPA, and rest of them fall under biovar 2, so to speak UUR. On the other hand strains that have not been clear in classification are more segmented and 5 more strains have been discovered7) (Table 1). Accordingly, authors should discuss the difference between UPA and UUR serovars first to claim that there was no difference in bronchopulmonary dysplasia (BPD) incidence in each servoar. It seems misleading that they say there was no difference according to BPD and serovars because their study had very limited subjects and approximately 1/3 had mixed serovars. Additionally, some investigators consider these mixed strains 475 http://dx.doi.org/10.3345/kjp.2013.56.11.474Korean J Pediatr 2013;56(11):474-476as totally different serovars according to hybridization and wonder if studies investigating difference among serovars are meaningless8). Although it is one of major conclusions of Eun and et al.6) that there is no difference between UUR serovars, the conclusion is not well established and it is better to get to a conclusion after experiments using UPA and UUR together.Ureaplasma is known as a strain difficult to culture in the laboratory because it is very small such as 15–25 micrometer diameter and has no cell wall. This strain produces adenosine triphosphate through urea hydrolysis and dissolves urea into ammonia (NH3) and carbon gas. When culturing in the labo-ratory, infection is judged through pH change in liquid culture using such principle. But recently, as studies have shown that PCR method is more sensitive, PCR method is preferred to classical culture1-3). To make more explanations on culture and PCR method, authors perform tracheal aspiration and gastric aspiration at the same time to identify correlations with BPD. As tracheal aspiration samples show whether there is lower respiratory colonization, which means infection in most cases, and may judge infection of Ureaplasma spp regardless of skills of testers, it is the most preferred method. However, it has a drawback that sampling can be made in newborns only with intubation. A probable alternative is nasopharyngeal swab. It is easy to get samples and can be repeated many times, although some authors said that we cannot judge infection only with the result of this test showing upper respiratory colonization1,2). Interestingly, in Eun et al.6) study, UUR serovar 9 is found to be the most common serovar, which was deal with Koreans. Whereas Sung et al.9) studies on Caucasians and African-Americans found that serovar 11 was the most common. Such difference may imply difference between races, although it must be confirmed with further studies, because of small sample size of this study. In particular, as there have not been many studies regarding the difference between races, it will be an interesting field to perform a large-scale study including gene tests. Many studies on relationship between Ureaplasma spp and complications of premature babies have been made recently and results are being published constantly. Among them, mechanism to make BPD by Ureaplasma spp. is considered as being made by activation of proinflammatory cytokines (tumor necrosis factor-α, interleukin [IL] 1β, IL-8) or blocking counterregulatory cytokines (IL-6, IL-10) rather than making direct damages on respiratory tract. There is a hypothesis that respiratory diseases and BPD of newborns are caused by phospholipase A2 created by other strains which coerces the creation of pulmonary surface activators. It is also know that infection in prenatal period stimulates infection consecutive infection of pulmonary alveoli, interferes the creation of pulmonary alveoli by directly or indirectly influencing respirator induced pulmonary damages, stimulates phagocytes composing cilliary disarray and clumping after composing colony on epithelial cells on respiratory tracts, and creates proinflammatory cytokine to cause BPD1,10,11). Such Table 1. Overview of Ureaplasma urealyticum and Ureaplasma parvum genomesSerovar ATCC GenBankaccession PFGE size (kbp) Genome size (bp) Contigs ORFs Hypothetical proteins % GC Sequence coverage1 27813 NZ_ABES00000000 760 753,674 8 604 212 25% 14.6X3 27815 NC_010503 760 751,679 1 609 219 25% 10.2X3 700970 NC_002162 Patient  isolate 751,719 1 614 154 25% -6 27818 NZ_AAZQ00000000 760 772,971 5 619 221 25% 11.4X14 33697 NZ_ABER00000000 760 749,965 7 594 199 25% 14.5X2 27814 NZ_ABFL00000000 880 861,061 1 664 248 26% 10.7X4 27816 NZ_AAYO00000000 910 835,413 4 654 206 26% 7.0X5 27817 NZ_AAZR00000000 1140 884,046 18 677 252 26% 8.5X7 27819 NZ_AAYP00000000 880 875,530 4 660 246 26% 8.3X8 27618 NZ_AAYN00000000 890 874,381 1 673 232 26% 9.9X9 33175 NZ_AAYQ00000000 950 947,165 10 711 244 26% 8.6X10 33699 NC_011374 890 874,478 1 657 232 26% 12.1X11 33695 NZ_AAZS00000000 840 876,474 6 644 236 27% 10.0X12 33696 NZ_AAZT00000000 870 873,466 2 650 234 25% 9.0X13 33698 NZ_ABEV00000000 900 846,596 5 655 234 25% 11.1X2033 Unknown serovar AJFX00000000 Patient  isolate 804,560 16 646 190 26% 39.0X2608 Unknown serovar AJFY00000000 Patient  isolate 856,546 14 667 258 26% 60.0X4155 Unknown serovar AJFZ00000000 Patient  isolate 858,890 18 684 225 26% 73.0X4318 Unknown serovar AJGA00000000 Patient  isolate 844,630 16 662 214 26% 52.0XPFGE, pulsed-field Gel Electrophoresis; ORF, open-reading frame; GC, guanine-cytosine.http://dx.doi.org/10.3345/kjp.2013.56.11.474Sung TJ • Ureaplasma Urealyticum or Ureaplasma Parvum 476relationship with cytokines should be studied further in the future.  Conclusively, more studies are needed on the relationship between Ureaplasam and infection of newborns, in particular complications of premature babies including BPD. It is also needed to perform a large scale study on Korean newborns. Conflict of interestNo potential conflict of interest relevant to this article was reported.  References 1. Waites KB, Katz B, Schelonka RL. Mycoplasmas and ureaplasmas as neonatal pathogens. Clin Microbiol Rev 2005;18:757-89. 2. Viscardi RM. Ureaplasma species: role in diseases of prematurity. Clin Perinatol 2010;37:393-409. 3. Sung TJ. Ureaplasma infections in pre-term infants: recent infor-mation regarding the role of Ureaplasma species as neonatal pathogens. Korean J Pediatr 2010;53:989-93. 4. Lim IS, Choi CW, Kim BI, Kim SD, Lee JA, Kim EK, et al. Clinical manifestations of Ureaplasma urealyticum colonization in infants.  Korean J Perinatol 2007;18:37-45. 5. Chang JY, Park YS, Shim GS, Bae CW, Seol HJ. The clinical features of the infants born from mothers with genital Ureaplasma urealyticum colonization. Korean J Perinatol 2010;21:288-97. 6. Eun HS, Lee SM, Park MS, Park KI, Namgung R, Lee C. Serological investigation of Ureaplasma urealyticum in Korean preterm infants. Korean J Pediatr 2013;56;477-81. 7. Paralanov V, Lu J, Duffy LB, Crabb DM, Shrivastava S, Methe BA, et al. Comparative genome analysis of 19 Ureaplasma urealyticum and Ureaplasma parvum strains. BMC Microbiol 2012;12:88. 8. Xiao L, Paralanov V, Glass JI, Duffy LB, Robertson JA, Cassell GH, et al. Extensive horizontal gene transfer in ureaplasmas from humans questions the utility of serotyping for diagnostic purposes. J Clin Microbiol 2011;49:2818-26. 9. Sung TJ, Xiao L, Duffy L, Waites KB, Chesko KL, Viscardi RM. Frequency of ureaplasma serovars in respiratory secretions of preterm infants at risk for bronchopulmonary dysplasia. Pediatr Infect Dis J 2011;30:379-83.10. Viscardi RM, Hasday JD. Role of Ureaplasma species in neonatal chronic lung disease: epidemiologic and experimental evidence. Pediatr Res 2009;65(5 Pt 2):84R-90R.11. Kallapur SG, Kramer BW, Jobe AH. Ureaplasma and BPD. Semin Perinatol 2013;37:94-101.

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