Absence of dihydropteroate synthase gene mutations in Pneumocystis jirovecii isolated from Swedish patients.

Pneumocystis jirovecii remains an important cause of pneumonia in the immunocompromised host, with the largest group of patients at risk for P. jirovecii pneumonia (PCP) in Sweden being those with haematological diseases. Widespread prophylaxis and treatment for P. jirovecii with sulfa-containing drugs have effectively decreased the incidence of PCP, but concerns have been raised about the possible emergence of P. jirovecii isolates that are resistant to these drugs. Two point mutations in the gene coding for the dihydropteroate synthase enzyme (DHPS) in P. jirovecii have been shown to be associated with prior exposure to sulfa drugs. We retrospectively studied the occurrence of P. jirovecii DHPS mutations in isolates recovered from 103 Swedish patients. The DHPS gene, including the polymorphic positions 165 and 171, were amplified and sequenced by pyrosequencing technology. All the clinical specimens showed a wild-type pattern indicating that the occurrence of P. jirovecii DHPS mutations in Sweden is very low or absent.

[1]  M. Lebbad,et al.  A limited number of ITS haplotypes defines the diversity of Pneumocystis jirovecii strains in Sweden. , 2011, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[2]  E. Calderón,et al.  Pneumocystis jiroveci Dihydropteroate Synthase Gene Mutations among Colonized Individuals and Pneumocystis Pneumonia Patients from Spain , 2010, Postgraduate medicine.

[3]  S. Meshnick,et al.  Prevalence of dihydropteroate synthase genotypes before and after the introduction of combined antiretroviral therapy and their influence on the outcome of Pneumocystis pneumonia in HIV-1-infected patients. , 2010, Diagnostic microbiology and infectious disease.

[4]  J. Frean,et al.  High Prevalence of Dihydropteroate Synthase Mutations in Pneumocystis jirovecii Isolated from Patients with Pneumocystis Pneumonia in South Africa , 2010, Journal of Clinical Microbiology.

[5]  D. Stark,et al.  Clinical Significance and Phylogenetic Relationship of Novel Australian Pneumocystis jirovecii Genotypes , 2009, Journal of Clinical Microbiology.

[6]  S. Meshnick,et al.  Pneumocystis jirovecii pneumonia in Spanish HIV-infected patients in the combined antiretroviral therapy era: prevalence of dihydropteroate synthase mutations and prognostic factors of mortality. , 2008, Diagnostic microbiology and infectious disease.

[7]  F. Antunes,et al.  Pneumocystis jirovecii multilocus genotyping profiles in patients from Portugal and Spain. , 2008, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[8]  G. Fantoni,et al.  Genotyping of Pneumocystis jiroveci Pneumonia in Italian AIDS Patients: Clinical Outcome Is Influenced by Dihydropteroate Synthase and Not by Internal Transcribed Spacer Genotype , 2007, Journal of acquired immune deficiency syndromes.

[9]  C. Beard,et al.  Pneumocystis jirovecii Dihydropteroate Synthase Gene Mutations and Human Immunodeficiency Virus‐Associated Pneumocystis Pneumonia , 2006, The Journal of eukaryotic microbiology.

[10]  J. Prolla,et al.  Absence of Dihydropteroate Synthase Mutations in Pneumocystis jirovecii from Brazilian AIDS Patients , 2006, The Journal of eukaryotic microbiology.

[11]  C. Beard,et al.  Severity and outcome of HIV-associated Pneumocystis pneumonia containing Pneumocystis jirovecii dihydropteroate synthase gene mutations , 2005, AIDS.

[12]  S. Meshnick,et al.  Sulfa Use, Dihydropteroate Synthase Mutations, and Pneumocystis jirovecii Pneumonia , 2004, Emerging infectious diseases.

[13]  S. Meshnick,et al.  Increase in prevalence of Pneumocystis carinii mutations in patients with AIDS and P. carinii pneumonia, in the United States and China. , 2004, The Journal of infectious diseases.

[14]  E. Maury,et al.  Pneumocystis jirovecii dihydropteroate synthase genotypes in French patients with pneumocystosis: a 1998-2001 prospective study. , 2003, Medical mycology.

[15]  F. Antunes,et al.  Mutations in the dihydropteroate synthase gene of Pneumocystis jiroveci isolates from Portuguese patients with Pneumocystis pneumonia. , 2003, International journal of antimicrobial agents.

[16]  Jacques Bille,et al.  Association between a specific Pneumocystis jiroveci dihydropteroate synthase mutation and failure of pyrimethamine/sulfadoxine prophylaxis in human immunodeficiency virus-positive and -negative patients. , 2003, The Journal of infectious diseases.

[17]  J. Kovacs,et al.  Mutations in the dihydropteroate synthase gene of human-derived Pneumocystis carinii isolates from Italy are infrequent but correlate with prior sulfa prophylaxis. , 2002, The Journal of infectious diseases.

[18]  K. Sepkowitz Opportunistic infections in patients with and patients without Acquired Immunodeficiency Syndrome. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[19]  S. Meshnick,et al.  New insights into transmission, diagnosis, and drug treatment of Pneumocystis carinii pneumonia. , 2001, JAMA.

[20]  C. Beard,et al.  Sulfa or sulfone prophylaxis and geographic region predict mutations in the Pneumocystis carinii dihydropteroate synthase gene. , 2000, The Journal of infectious diseases.

[21]  Yoshikazu Nakamura,et al.  Relationship between Mutations in Dihydropteroate Synthase of Pneumocystis carinii f. sp.hominis Isolates in Japan and Resistance to Sulfonamide Therapy , 2000, Journal of Clinical Microbiology.

[22]  S. Meshnick,et al.  Pneumocystis carinii mutations are associated with duration of sulfa or sulfone prophylaxis exposure in AIDS patients. , 2000, The Journal of infectious diseases.

[23]  Ola Sköld,et al.  Sulfonamide resistance: mechanisms and trends. , 2000, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[24]  C. Beard,et al.  Genetic variation in Pneumocystis carinii isolates from different geographic regions: implications for transmission. , 2000, Emerging infectious diseases.

[25]  J. Lundgren,et al.  Effects of mutations in Pneumocystis carinii dihydropteroate synthase gene on outcome of AIDS-associated P carinii pneumonia , 1999, The Lancet.

[26]  M. Kai [Diaminodiphenylsulfone resistance of Mycobacterium leprae due to mutations in the dihydropteroate synthase gene]. , 1999, Nihon Hansenbyo Gakkai zasshi = Japanese journal of leprosy : official organ of the Japanese Leprosy Association.

[27]  S. Meshnick,et al.  Pneumocystis carinii mutations associated with sulfa and sulfone prophylaxis failures in AIDS patients , 1998, AIDS.

[28]  M. Page,et al.  Structure and function of the dihydropteroate synthase from Staphylococcus aureus. , 1997, Journal of molecular biology.

[29]  J. E. Hyde,et al.  Sulfadoxine resistance in the human malaria parasite Plasmodium falciparum is determined by mutations in dihydropteroate synthetase and an additional factor associated with folate utilization , 1997, Molecular microbiology.

[30]  W. Dallas,et al.  Cloning, sequencing, and enhanced expression of the dihydropteroate synthase gene of Escherichia coli MC4100 , 1992, Journal of bacteriology.

[31]  A. Hjerpe,et al.  Pneumocystis carinii pneumonia: detection of parasites in sputum and bronchoalveolar lavage fluid by monoclonal antibodies. , 1988, BMJ.