Mutational Analysis of Pneumocystis jirovecii Dihydropteroate Synthase and Dihydrofolate Reductase Genes in HIV-Infected Patients in China

Deng, Xianwen; Li, Zhuo; Lan, Yun; Dai, Zhaoxia; Chen, Wanshan; Cai, Weiping; Kovacs, Joseph A.; Ma, Liang; Tang, Xiaoping

doi:10.1128/jcm.01848-14

Cited by 10 publications

(9 citation statements)

References 14 publications

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“…Furthermore, the rates of DHPS and DHFR mutations were still very low [12,[35][36][37]. In this study, DHPS WT and DHFR 312C were observed at the DHPS and DHFR locus and no other mutations were detected, consistent with the prior studies reported in PR China [12,34,37]. This low prevalence of DHPS and DHFR mutations was not only demonstrated in China but also in other developing countries such as Brazil, South Africa and Thailand [38][39][40].…”

Section: Discussionsupporting

confidence: 90%

“…Several previous studies have demonstrated that treatment failures of PJP are closely correlated with the high mutation rates of DHPS and DHFR gene and the frequencies of mutations in DHPS gene are greatly higher than that in DHFR, indicating that the DHPS mutations are caused by the pressure of drug selection but not random occurrences [31,32]. The DHPS wild-type (WT) sequence was more frequent displaying in P. jirovecii DHPS genotype, while WT and DHFR 312 synonymous mutations (nucleotides at position 312C) were common in DHFR genotype [7,33,34].…”

Section: Discussionmentioning

confidence: 99%

“…The synonymous mutations in DHFR genotypes are probably based on polymorphisms rather than the pressure for drug selection [1,34]. Furthermore, the rates of DHPS and DHFR mutations were still very low [12,[35][36][37].…”

Section: Discussionmentioning

confidence: 99%

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Genetic Polymorphisms of 3 Cases Pneumocystis jirovecii in Shanxi Province PR China

Xue

Du²,

Dai

et al. 2021

Preprint

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Background Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungus and is a well-known cause of potentially fatal Pneumocystis jirovecii pneumonia (PJP). However, the epidemiology and biology of P. jirovecii is limited because of the lack of a continuous and reliable culture system in vitro. This study was performed with the objectives of investigating the genetic polymorphisms of P. jirovecii from 3 cases in Shanxi Province PR China with the utilizations of molecular biological technique.Methods Analysis of genetic polymorphisms in P. jirovecii including the internal transcribed spacer regions of rRNA operon (ITS), superoxide dismutase (SOD), dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR), cytochrome b (CYB) and the mitochondrial large-subunit rRNA (mt LSU rRNA) genes were performed by Nested-PCR amplification, TA clone, sequencing and genotyping. We assessed its correlation with clinical characteristics of patients with P. jirovecii pneumonia (PJP). Results Of three patients with PJP included in the present study, the genetic diversities and polymorphic combinations of SOD 1, DHFR 312C, DHPS WT, mt3 genotypes separately occurred in the two HIV-positive patients, while coinfections with two genotypes of P. jirovecii in the same patient without HIV were detected for different genetic loci including ITS, SOD, CYB and mt LSU rRNA in this study. The pulmonary concurrent infection with other pathogens was detected in this HIV-negative patient.Conclusions The present study is the first analyzed and assessed the genetic polymorphisms of 3 cases P. jirovecii in Shanxi province PR China suggesting that genetic diversities and concurrent infection with other pathogens were possibly associated with the clinical characteristics and outcomes in PJP patients especially those without HIV.Trial registration Not applicable.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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Genetic Polymorphisms of 3 Cases Pneumocystis jirovecii in Shanxi Province PR China

Xue

Du²,

Dai

et al. 2021

Preprint

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“…There is increasingly convincing evidence from genotyping studies supporting recent acquisition in at least some cases. This includes the presence of different genotypes between the first and second episodes in patients with recurrent infection (366,524,525); outbreaks of PCP caused by a single strain within one or more organ transplant centers, based on highly discriminative msg-RFLP or MLST, as discussed below (355,357,526,527); and the occurrence of sulfa resistance-associated dhps mutations in patients without prior exposure to sulfa drugs (54,57,528,529). Recent acquisition is further supported by the high prevalence of multistrain coinfections as discussed in the preceding section.…”

Section: Strain Variation Of P Jiroveciimentioning

confidence: 99%

A Molecular Window into the Biology and Epidemiology of Pneumocystis spp

2018

Self Cite

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, a unique atypical fungus with an elusive lifestyle, has had an important medical history. It came to prominence as an opportunistic pathogen that not only can cause life-threatening pneumonia in patients with HIV infection and other immunodeficiencies but also can colonize the lungs of healthy individuals from a very early age. The genus includes a group of closely related but heterogeneous organisms that have a worldwide distribution, have been detected in multiple mammalian species, are highly host species specific, inhabit the lungs almost exclusively, and have never convincingly been cultured, making a fascinating but difficult-to-study organism. Improved molecular biologic methodologies have opened a new window into the biology and epidemiology of. Advances include an improved taxonomic classification, identification of an extremely reduced genome and concomitant inability to metabolize and grow independent of the host lungs, insights into its transmission mode, recognition of its widespread colonization in both immunocompetent and immunodeficient hosts, and utilization of strain variation to study drug resistance, epidemiology, and outbreaks of infection among transplant patients. This review summarizes these advances and also identifies some major questions and challenges that need to be addressed to better understand biology and its relevance to clinical care.

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“…This result is consistent with those of previous studies of Chinese people. Kazanjian et al revealed a DHPS gene mutation rate of 6.7% (1/15) in AIDS-PCP in Beijing[ 30 ], Deng et al identified DHPS mutations in 12.0% (3/25) patients from Guangzhou[ 31 ], the prevalence of P . jirovecii DHPS mutations in this study is not significantly higher than those of these previous studies ( P = 0.858, P = 0.137, respectively).…”

Section: Discussionmentioning

confidence: 99%

Clinical characteristics and prevalence of dihydropteroate synthase gene mutations in Pneumocystis jirovecii-infected AIDS patients from low endemic areas of China

Zhu

2020

PLoS ONE

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Pneumocystis pneumonia (PCP) is an opportunistic and potentially life-threatening infection of AIDS patients caused by the fungus Pneumocystis jirovecii (P. jirovecii). Trimethoprimsulfamethoxazole (TMP-SMX) is the most commonly used drug combination in the treatment and prophylaxis of PCP. However, with long-term use of this combination, mutations in the dihydropteroate synthase (DHPS) gene of P. jirovecii bring about the development of resistance. Data on the prevalence of P. jirovecii and its DHPS mutants in China, especially in low endemic areas, are still limited. Thus, in the present study, we measured the P. jirovecii infection rate among HIV-positive and AIDS (HIV/AIDS) patients with suspected PCP and investigated the relationship between CD4 + T cell count and PCP occurrence. As well as the polymerase chain reaction (PCR) analysis and sequencing, the restriction fragment length polymorphism (RFLP) method was used to analyze DHPS point mutation in P. jirovecii strains. P. jirovecii was detected in 40.82% of cases. The clinical symptoms and signs of PCP were not typical; with decreasing CD4 + T cell counts, PCP infection in HIV/AIDS patients increased. In only one case (1.67%), the patients' DHPS gene could not be cut by the Acc I restriction enzyme. Furthermore, mutation at codon 171 was detected in 11 cases and no mutation was found at codon 57. Patients treated with sulfamethoxazole combined with Voriconazole or Caspofungin exhibited favorable results. After treatment, the symptoms of dyspnea were alleviated, and chest computed tomography findings showed the improvement of lung shadows. These indicated that the prevalence of DHPS mutations in P. jirovecii isolates in AIDS-PCP patients in the region was low. Thus, the contribution of gene mutations to treatment failure requires further research.

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Mutational Analysis of Pneumocystis jirovecii Dihydropteroate Synthase and Dihydrofolate Reductase Genes in HIV-Infected Patients in China

Cited by 10 publications

References 14 publications

Genetic Polymorphisms of 3 Cases Pneumocystis jirovecii in Shanxi Province PR China

Genetic Polymorphisms of 3 Cases Pneumocystis jirovecii in Shanxi Province PR China

A Molecular Window into the Biology and Epidemiology of Pneumocystis spp

Clinical characteristics and prevalence of dihydropteroate synthase gene mutations in Pneumocystis jirovecii-infected AIDS patients from low endemic areas of China

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