The Relationship Between Ureaplasma Species and Male Infertility: Pathogenicity, Biology, Diagnosis, and Treatment.

Objective: Ureaplasma spp. comprise a group of mycoplasmas containing two human-associated species, namely, Ureaplasma urealyticum (UUR) and Ureaplasma parvum (UPA). The characterization of Ureaplasma species as pathogens contributing to male infertility remains a subject of considerable controversy. While numerous authors have proposed a relationship between UUR and changes in fertility, there is limited evidence supporting the involvement of UPA in this context. There has been an increased focus on Ureaplasma spp. and its potential role in the development of male infertility, especially over the past few years. The review aims to clarify the relationship between Ureaplasma species and male infertility. Methods: Firstly, we introduce a background of the appropriate biology including growth characteristics, the divided biovars, and the transmission pathways. Secondly, we examine the studies that support a causal role for Ureaplasma spp. in the development of infertility in the last 30 years. Finally, the diagnosed method, antimicrobial susceptibility, and potential therapeutic considerations are evaluated. Results: UPA and UUR can impair semen motility. The species of Ureaplasma spp., the sexual history of the patient, the number of sexual partners, the load of Ureaplasma, and antimicrobial resistance are expected to constitute key risk factors in the development of male infertility. In terms of treatment, Doxycycline remains the drug of first choice for ureaplasmal infections. Conclusion: Ureaplasma spp. are not simply "innocent bystanders" in infertility and may indeed be an "underestimated enemy of human reproduction". Ureaplasma spp. can be considered an etiological agent in unexplained infertility and a useful marker.

Comparative Analysis of Herbaceous and Woody Cell Wall Digestibility by Pathogenic Fungi.

Fungal pathogens have evolved combinations of plant cell-wall-degrading enzymes (PCWDEs) to deconstruct host plant cell walls (PCWs). An understanding of this process is hoped to create a basis for improving plant biomass conversion efficiency into sustainable biofuels and bioproducts. Here, an approach integrating enzyme activity assay, biomass pretreatment, field emission scanning electron microscopy (FESEM), and genomic analysis of PCWDEs were applied to examine digestibility or degradability of selected woody and herbaceous biomass by pathogenic fungi. Preferred hydrolysis of apple tree branch, rapeseed straw, or wheat straw were observed by the apple-tree-specific pathogen Valsa mali, the rapeseed pathogen Sclerotinia sclerotiorum, and the wheat pathogen Rhizoctonia cerealis, respectively. Delignification by peracetic acid (PAA) pretreatment increased PCW digestibility, and the increase was generally more profound with non-host than host PCW substrates. Hemicellulase pretreatment slightly reduced or had no effect on hemicellulose content in the PCW substrates tested; however, the pretreatment significantly changed hydrolytic preferences of the selected pathogens, indicating a role of hemicellulose branching in PCW digestibility. Cellulose organization appears to also impact digestibility of host PCWs, as reflected by differences in cellulose microfibril organization in woody and herbaceous PCWs and variation in cellulose-binding domain organization in cellulases of pathogenic fungi, which is known to influence enzyme access to cellulose. Taken together, this study highlighted the importance of chemical structure of both hemicelluloses and cellulose in host PCW digestibility by fungal pathogens.

In vitro activities of acetylmidecamycin and other antimicrobials against human macrolide-resistant Mycoplasma pneumoniae isolates.

OBJECTIVES: To assess the in vitro activities of acetylmidecamycin, a 16-membered macrolide, and 11 other antimicrobial agents against human mycoplasmas. METHODS: A total of 187 clinical isolates, Mycoplasma pneumoniae (n = 110), Mycoplasma hominis (n = 26) and Ureaplasma species (n = 51), were included in this study. The MICs of 12 antimicrobial agents, including acetylmidecamycin, thiamphenicol, chloramphenicol and some other macrolides, fluoroquinolones and tetracyclines, for these clinical isolates were determined by the broth microdilution method. RESULTS: For M. pneumoniae, the MIC90 values of the tested macrolides were: acetylmidecamycin (1 mg/L)128 mg/L). Thiamphenicol and chloramphenicol had the same MIC90 (2 mg/L). For Ureaplasma species, the MIC90 values were: acetylmidecamycin (0.25 mg/L)128 mg/L)=erythromycin. The MIC90 values of chloramphenicol and thiamphenicol were 2 and 4 mg/L, respectively. CONCLUSIONS: The results indicated that acetylmidecamycin and thiamphenicol are active in vitro against the most common mycoplasma species infecting humans, including those resistant to macrolides and fluoroquinolones. Acetylmidecamycin and thiamphenicol might be a promising option for clinicians to treat infections caused by Mycoplasma and Ureaplasma spp., particularly macrolide-resistant M. pneumoniae in paediatrics and fluoroquinolone-resistant M. hominis in adults. Further investigation of their clinical roles in treating infections caused by these organisms is warranted.

Bioinformatics Analysis and Characterization of Highly Efficient Polyvinyl Alcohol (PVA)-Degrading Enzymes from the Novel PVA Degrader Stenotrophomonas rhizophila QL-P4.

Polyvinyl alcohol (PVA) is used widely in industry, and associated environmental pollution is a serious problem. Herein, we report a novel, efficient PVA degrader, Stenotrophomonas rhizophila QL-P4, isolated from fallen leaves from a virgin forest in the Qinling Mountains. The complete genome was obtained using single-molecule real-time (SMRT) technology and corrected using Illumina sequencing. Bioinformatics analysis revealed eight PVA/vinyl alcohol oligomer (OVA)-degrading genes. Of these, seven genes were predicted to be involved in the classic intracellular PVA/OVA degradation pathway, and one (BAY15_3292) was identified as a novel PVA oxidase. Five PVA/OVA-degrading enzymes were purified and characterized. One of these, BAY15_1712, a PVA dehydrogenase (PVADH), displayed high catalytic efficiency toward PVA and OVA substrate. All reported PVADHs only have PVA-degrading ability. Most importantly, we discovered a novel PVA oxidase (BAY15_3292) that exhibited higher PVA-degrading efficiency than the reported PVADHs. Further investigation indicated that BAY15_3292 plays a crucial role in PVA degradation in S. rhizophila QL-P4. Knocking out BAY15_3292 resulted in a significant decline in PVA-degrading activity in S. rhizophila QL-P4. Interestingly, we found that BAY15_3292 possesses exocrine activity, which distinguishes it from classic PVADHs. Transparent circle experiments further proved that BAY15_3292 greatly affects extracellular PVA degradation in S. rhizophila QL-P4. The exocrine characteristics of BAY15_3292 facilitate its potential application to PVA bioremediation. In addition, we report three new efficient secondary alcohol dehydrogenases (SADHs) with OVA-degrading ability in S. rhizophila QL-P4; in contrast, only one OVA-degrading SADH was reported previously.IMPORTANCE With the widespread application of PVA in industry, PVA-related environmental pollution is an increasingly serious issue. Because PVA is difficult to degrade, it accumulates in aquatic environments and causes chronic toxicity to aquatic organisms. Biodegradation of PVA, as an economical and environment-friendly method, has attracted much interest. To date, effective and applicable PVA-degrading bacteria/enzymes have not been reported. Herein, we report a new efficient PVA degrader (S. rhizophila QL-P4) that has five PVA/OVA-degrading enzymes with high catalytic efficiency, among which BAY15_1712 is the only reported PVADH with both PVA- and OVA-degrading abilities. Importantly, we discovered a novel PVA oxidase (BAY15_3292) that is not only more efficient than other reported PVA-degrading PVADHs but also has exocrine activity. Overall, our findings provide new insight into PVA-degrading pathways in microorganisms and suggest S. rhizophila QL-P4 and its enzymes have the potential for application to PVA bioremediation to reduce or eliminate PVA-related environmental pollution.

Clonal diversity of Ureaplasma species and its relationship with oligozoospermia and semen quality in Chinese infertile males.

Whether Ureaplasma spp. are a causative agent of male infertility remains controversial. Previous studies concerning Ureaplasma spp. and male infertility have been confined to the species level of Ureaplasma. Currently, an expanded multilocus sequence typing (eMLST) scheme has been established with high discriminatory power. The aim of this study was to use eMLST to explore the distribution of Ureaplasma spp. and to analyze its role in oligozoospermia and semen quality. A total of 480 semen samples were obtained from Chinese infertile males. The associations between Ureaplasma spp. with oligozoospermia and semen characteristics were further evaluated. Phylogenetic analysis revealed that 102 Ureaplasma spp. could be separated into two clusters and seven sub-groups. Within cluster I (U. parvum), eST16 and eST41 were the most frequent clones. For cluster II (U. urealyticum), eST82 and eST147 were the most prevalent clones. Sub-groups A and C belonging to cluster I and sub-group 1 belonging to cluster II showed an association with oligozoospermia, in contrast with the Ureaplasma spp. negative group (P < 0.05). Compared with the negative group, semen motility decreased in sub-group 2, especially for non-progressive motility (P < 0.05). These results indicated that sub-groups A and C belonging to cluster I (U. parvum) and sub-group 1 belonging to cluster II (U. urealyticum) were shown to be associated with oligozoospermia. Sub-group 2 belonging to cluster II may have the ability to impair semen motility, especially for non-progressive motility.

Phenotypic Antimicrobial Susceptibility and Genotypic Characterization of Clinical Ureaplasma Isolates Circulating in Shanghai, China.

There is a growing global concern regarding the rise of antimicrobial resistance among Ureaplasma spp. isolates. However, studies on the antimicrobial susceptibility profiles, resistance mechanisms, and clonality of Ureaplasma spp. clinical isolates are still limited and cover only some geographic regions. Firstly, Ureaplasma species from the urogenital tracts of patients in Shanghai, China, were isolated by using the culture medium (A8 and 10B broth), and identified the genotype by polymerase chain reaction (PCR). Secondly, the antimicrobial susceptibility tests were determined by using broth microdilution assay. Then, the resistance genetic determinants to fluoroquinolones (FQs), macrolides, and tetracyclines were investigated through PCR/DNA sequencing. Finally, the molecular epidemiology of Ureaplasma species was studied by multilocus sequence typing (MLST). Among 258 isolates, Ureaplasma parvum (UPA) and Ureaplasma urealyticum (UUR) were found in 226 (87.60%) and 32 (12.40%) isolates, respectively. The minimum inhibitory concentrations (MICs) of 258 Ureaplasma spp. strains ranged from 0.015 to 64µg/ml for all 11 kinds of antimicrobials. Regardless of species, the isolates were most sensitive to AZI (1.94%), JOS (3.49%), and CLA (4.23%). Among them, there were 39 (15.12%) multidrug-resistant (MDR) strains, including 32 UPA isolates. The resistance rates of UPA to CIP (91.59%), and ROX (36.28%) were significantly higher than those of UUR. Twenty six FQ-resistant isolates had amino acid substitutions in gyrA and in parC (Ser83Leu). Mutations were detected in genes encoding ribosomal proteins L4 (Thr84Ile) and L22 (Ser81Pro) in macrolide-resistant isolates. Tet(M) was found in four UPA isolates. These mutations were mainly found in UPA isolates. Sequence type 1 (ST1) was the predominant ST, which contained 18 isolates. In conclusion, this study showed a higher resistance rate (especially to ROX and CIP), higher substitution rate, and higher MDR rate among UPA strains. The most active antimicrobial agents were AZI, JOS, and CLA. Identifying UPA or UUR in clinical isolates could help clinicians to choose appropriate drugs for treatment. The main resistance mechanisms may involve gene substitution of Ser83Leu in parC and Ser81Pro in L22. ST1 was the predominant ST of Ureaplasma isolates with MDR to FQs and macrolides in Shanghai, China.

In vitro Activities of Nemonoxacin and Other Antimicrobial Agents Against Human Mycoplasma and Ureaplasmas Isolates and Their Defined Resistance Mechanisms.

Nemonoxacin, a newly developed non-fluorinated quinolone (NFQ), selectively inhibits bacterial DNA topoisomerase activity. However, its activities against Mycoplasmas have rarely been studied to date. Herein, the activities of nemonoxacin were evaluated against clinical isolates of 50 Mycoplasma pneumoniae, 20 Mycoplasma hominis, and 77 Ureaplasma spp., and they were compared to fluoroquinolones, tetracyclines, and macrolides. Nemonoxacin MICs (µg/ml) ranged from 0.03 to 0.25 for M. pneumoniae, 0.25 to 8 for M. hominis, and 0.06 to >16 for Ureaplasma spp., and all of the ranges are similar to those of fluoroquinolones. The activity of nemonoxacin against Mycoplasmas was not affected by resistance to macrolides in the strains tested, but it seems to have the same resistant mechanism as fluoroquinolones. In addition, minimum bactericidal concentrations (MBC) of nemonoxacin to M. pneumoniae were within two dilutions of the MIC values, indicating a bactericidal effect on M. pneumoniae. Nemonoxacin merits further study for treating infections caused by these organisms.

Mitochondrial ultrastructure & release of proteins during liver regeneration.

BACKGROUND & OBJECTIVES: It has been reported that some proteins are released from mitochondria during liver regeneration after partial hepatectomy (PH), but the relationship between proteins release and mitochondrial permeability transition (MPT) remains unclear. We undertook this study to demonstrate the changes of mitochondrial ultrastructure and proteins release during liver regeneration and to determine the relationship between proteins release and MPT in liver regeneration in rats. METHODS: After PH and administration of cyclosporin-A (CsA, a specific inhibitor of MPT), ultrastructural morphology of mitochondria in the remnant liver were determined by electron microscopy. Catalytic activity of mitochondrial and cytosolic proteins including aspartate aminotransferase (AST) and glutamic acid dehydrogenase (GDH) was measured. RESULTS: The liver mitochondria at 24 and 72 h were quite variable in morphology and ultrastructure. The enzyme activities of AST and GDH in cytosol released from mitochondrial matrix changed significantly at 24 and 72 h. CsA can inhibit the permeability of mitochondria partly at the same time. INTERPRETATION & CONCLUSIONS: The changes of mitochondria in ultrastructure reflected the feature of MPT, and the changes of enzymes activities released from mitochondrial matrix were consistent with those of mitochondrial ultrastructure. CsA can inhibit these changes to some extent. There was a close relationship of MPT with mitochondrial ultrastructure and proteins release during liver regeneration.

Comamonas kerstersii bacteremia in a patient with acute perforated appendicitis: A rare case report.

RATIONALE: Comamonas species are rarely associated with human infections. Recent reports found that Comamonas kerstersii was associated with severe diseases such as abdominal infection and bacteremia. However, C. kerstersii maybe be confused with Comamonas testosteroni using the automatic bacterial identification systems currently available. PATIENT CONCERNS: A 31-year-old man who had onset of left upper abdominal pain developed clinical manifestations of right lower abdominal pain and classic migration of pain at the temperature of 39°C. The positive strain of aerobic and anaerobic bottles of blood cultures was identified. DIAGNOSES: The patient was diagnosed as acute peritonitis and perforated appendix with abdominal abscess. INTERVENTIONS: The bacterium was identified by routine methods, MALDI-TOF-MS and PCR amplification of the 16S rRNA. The patient was treated with exploratory laparotomy, appendectomy, tube drainage, and prescribing antibiotic treatment. OUTCOMES: The patients were discharged with complete recovery. The organisms were confirmed as C. kerstersii by MALDI-TOF-MS and a combination of the other results. LESSONS: Our findings suggest that C. kerstersii infection occurs most often in association with perforated appendix and bacteremia. We presume that C. kerstersii is an opportunistic pathogen or commensal with the digestive tract and appendix bacteria.

Down-regulation of miR-23b may contribute to activation of the TGF-ß1/Smad3 signalling pathway during the termination stage of liver regeneration.

MicroRNAs (miRNAs) are known to play important roles in liver regeneration, although the role of miRNAs associated with the termination of liver regeneration is not as well studied. Here we reported the down-regulation of miR-23b in the termination stage of liver regeneration in rats. In addition, Smad3 was identified as a target of miR-23b during liver regeneration. Up-regulation of miR-23b promoted BRL-3A cell proliferation and partially inhibited transforming growth factor (TGF)-ß1-induced apoptosis. Furthermore, TGF-ß1 transcriptionally inhibited miR-23b expression. We conclude that down-regulation of miR-23b may contribute to activation of the TGF-ß1/Smad3 signalling pathway during the termination stage of liver regeneration.

Siglec-1 on monocytes is a potential risk marker for monitoring disease severity in coronary artery disease.

OBJECTIVES: Siglec-1 has long been considered as an important biomarker of the activation of monocyte/macrophage and a type I interferon-specific imprint, but its role in atherosclerosis has not been elucidated. METHODS: We examined the expression of Siglec-1 by flow cytometry and RT-PCR in 83 CAD patients and 38 healthy controls. In addition, the levels of serum lipids, Gensini score, hs-CRP and homocysteine were determined. RESULTS: The transcriptional and protein levels of Siglec-1 on monocytes in CAD patients were significantly increased compared with healthy controls [3.17 versus 1.0, P<0.01; (11.5+/-3.9)% versus (1.8+/-2.0)%, P<0.01], but the increased Siglec-1 had no correlation with the level of native serum lipids. Interestingly, the expression of Siglec-1 was positively correlated with Gensini score (r=0.338, P=0.015), hs-CRP (r=0.316, P=0.016) and homocysteine level (r=0.224, P=0.042). CONCLUSION: Siglec-1 may be considered as a potential non-invasive indicator for monitoring disease severity and a biomarker for predicting the relative risk of cardiovascular events.