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Abstract
Pneumocystis pneumonia is a severe opportunistic infection in immunocompromised patients caused by the unusual fungus Pneumocystis jirovecii. Transmission is airborne, with both immunocompromised and immunocompetent individuals acting as a reservoir for the fungus. Numerous reports of outbreaks in renal transplant units demonstrate the need for valid genotyping methods to detect transmission of a given genotype. Here, we developed a short tandem repeat (STR)-based molecular typing method for P. jirovecii. We analyzed the P. jirovecii genome and selected six genomic STR markers located on different contigs of the genome. We then tested these markers in 106 P. jirovecii PCR-positive respiratory samples collected between October 2010 and November 2013 from 91 patients with various underlying medical conditions. Unique (one allele per marker) and multiple (more than one allele per marker) genotypes were observed in 34 (32%) and 72 (68%) samples, respectively. A genotype could be assigned to 55 samples (54 patients) and 61 different genotypes were identified in total with a discriminatory power of 0.992. Analysis of the allelic distribution of the six markers and minimum spanning tree analysis of the 61 genotypes identified a specific genotype (Gt21) in our hospital, which may have been transmitted between 10 patients including six renal transplant recipients. Our STR-based molecular typing method is a quick, cheap and reliable approach to genotype Pneumocystis jirovecii in hospital settings and is sensitive enough to detect minor genotypes, thus enabling the study of the transmission and pathophysiology of Pneumocystis pneumonia.
Highlights
Pneumocystis jirovecii is an unusual ubiquitous fungus that infects humans [1,2]
This notion has been confirmed epidemiologically by numerous Pneumocystis pneumonia (PCP) outbreaks resulting from intra-hospital transmission, especially in renal transplant units [13,14,15,16,17,18,19,20,21,22]
From a pathophysiological perspective, understanding transmission will help us to determine whether: (i) P. jirovecii remains dormant after the control of a primary infection in childhood and reactivates upon immunodeficiency [2,23]; or (ii) individuals are continuously exposed to P. jirovecii throughout life and achieve balance between clearance and exposure until the latest P. jirovecii genotype(s) leads to the development of PCP [1,2]
Summary
Pneumocystis jirovecii is an unusual ubiquitous fungus that infects humans [1,2]. From a pathophysiological perspective, understanding transmission will help us to determine whether: (i) P. jirovecii remains dormant after the control of a primary infection in childhood and reactivates upon immunodeficiency [2,23]; or (ii) individuals are continuously exposed to P. jirovecii throughout life and achieve balance between clearance and exposure until the latest P. jirovecii genotype(s) leads to the development of PCP [1,2]. These two hypotheses are not necessarily mutually exclusive.
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