Paracoccidioides brasiliensis
Classification
Higher order taxa
Eukaryota; Fungi; Ascomycota; Eurotiomycetes; Ongenales; Ajellomycetaecaea [1].
Description and Significance
Paracoccidiodomycosis brasiliensis is a dimorphic fungus with a yeast-like form. P. brasiliensis is endemic to Central and South America, particularly in humid subtropical areas, with 80% of reported cases occurring in Brazil [2]. It is responsible for paracoccidiodomycosis, primarily contracted through the inhalation of conidae [3], mostly affecting men who work outdoors in rural areas and children who are frequently outdoors. There have been more than 15,000 recorded cases of paracoccidiodomycosis since 1930, but there may be more cases as this disease is underrecognized [4]. There is less than a 5% death rate [5], yet the disease can cause severe complications for those with AIDS and HIV [6].
Genome Structure
The genome structure has not been fully sequenced. The genes arf and gp43 have been used to determine similarity between P. brasiliensis lineages in different regions. P. brasiliensis contains a MAT1 gene, known as a mating type locus, which allows these fungi to reproduce sexually. Their genome encodes a heterothallic relationship in which two compatible P. brasiliensis are required to reproduce [8]. The four lineages of P. brasiliensis, denoted (S1, PS2, PS3, PS4), differ by their differentiation of the nuclei from the parent P. brasiliensis while each maintaining an similar mitochondrial loci between them [9],[10]. This type of genetic similarity maintained within a species by mitochondrial DNA is a distinct artifact of P. brasiliensis and is supported by the common eukaryotic practice of mitochondrial introgression where these mitochondrial loci can crossover with each other in a way that makes the lineages more genomically similar [10].
Cell Structure
P. brasiliensis appears in spherical (yeast) cells (between 5 and 30uM diameter) and has a thick cell wall. Colonies of P. brasiliensis demonstrate a branched, septate, or hyphae-like structure. Ultrastructural studies reveal that yeast cells of P. brasiliensis contain multiple nuclei, and that the cells are aploid [2]. The cell wall of P. brasiliensis is a combination of polysaccharides and proteins which are directly impacted by the environment, in particular temperature, and the fungus’ natural cell cycle [11]. Certain sugars, specifically the ɑ-1,3-glucan, are important to the P. brasiliensis pathogenicity and dimorphic property [11]. The changes in sugar conformations allow P. brasiliensis to switch between different phases (Y and M) which have morphological and pathogenic differences. The Y and M phases are terms that describe different forms of the Cell Wall that carry different polysaccharides which impact pathogenicity [11]. Propagules, a vegetative structure within P. brasiliensis, can detach from plants and are a key structural cell component that is causal in paracoccidioidomycosis [12]. Conformational changes within the cell wall of P. brasiliensis, activated by temperature changes, impact its pathogenicity. This transformation is found to impact the glycan groups associated with the cell wall which help with avoiding a natural inflammatory response of the body [12].
Metabolic Processes
Paracoccidioides brasiliensis produces enzymes that drive the glycolytic pathway and tricarboxylic acids cycle, and also bind to the host cell’s extracellular matrix leading to infection [15]. As a pathogenic fungus, Paracoccidioides brasiliensis produces enzymes like superoxide dis-mutates and thioredoxins that nullify the damaging effect of oxidative and nitrosative stressor molecules induced by the host’s immune [15]. Paracoccidioides brasiliensis utilize MiRNA to lower oxidative phosphorylation activity in response to low iron availability [13]. During iron deprivation, Paracoccidioides brasiliensis can scavenge siderophores from the environment and use host proteins that have iron as a source of metal for their own metabolic activity [14].
Ecology
Paracoccidioides brasiliensis is widely found in South American countries, including Brazil, Colombia and Venezuela. It has been commonly discovered within soil samples and mammals such as the nine-banded armadillo and humans [16]. P. brasiliensis comprises four different lineages (S1, PS2, PS3, PS4) which all have varying levels of potential pathogenicity [9]. S1, has been identified as more pathogenic than the other lineages [9]. When infecting a human host, Paracoccidioides brasiliensis is capable of producing DNA ingesting enzymes escape from an immune system response known as neutrophil extracellular traps, which captures pathogenic microorganism with net-like tangles of DNA [17].
Pathology
Paracoccidioides brasiliensis is a dimorphic fungus found to be the cause of paracoccidioidomycosis (PCM), a systemic fungal infection of humans commonly found in Latin America [18], [19]. PCM most commonly infects the body through the respiratory tract, thus allowing P. brasiliensis to reach the lungs [20]. In PCM patients, P. brasiliensis is mostly detected in the lungs, upper respiratory tract mucosa, lymph nodes, and skin [21]. Infections by P. brasiliensis are separated into two forms, depending on the age and symptoms of the patient [20]. The acute/subacute form mainly affects children with lesions that are spread throughout the body. The chronic form mainly affects adult men with lesions in the oral mucosa, airways, and lungs [20]. Women are found to be protected against PCM through the presence of estrogen. However, in more recent studies, there is no significant gender-related difference in the severity of PCM [22].
Diagnosis and Treatment
Paracoccidioidomycosis can be detected by performing a biopsy, blood test, or through Fourier Transform Infrared spectroscopy (FTIR) [19]. To treat PCM, antifungal medicines can be used. Some examples of antifungal treatments to treat PCM include: amphotericin B, azoles, and sulfonamides derivatives [23].
Current Research
Current research on P. brasiliensis involves using its taxonomic classification and to influence the development of new treatment plans for those infected with Paracoccidiomycosis (PCM) [24]. This research began in 2020 after new sequencing studies reclassified P. brasiliensis into a new species, and learned that PCM is caused by three specific genotypes of Paracoccidiodes, one of which being P. brasiliensis [25]. Now, research is being conducted on how the three Paracoccidiodes genotypes are similar or different in their pathogenesis and how this affects the clinical outcomes of PCM. Along with this, researchers have been studying which strain of Paracoccidiodes has more of an effect on certain countries in Latin America that have higher populations of those infected with PCM. Current research has discovered that P. brasiliensis contains two lineages (S1a and S1b), and each lineage affects specific parts of Latin America, and is the only genotype that causes chronic PCM [25]. In a past study, researchers compared patients who had PCM and were co-infected with HIV to patients who live in an area where PCM regularly occurs (the control group) [26]. After studying these groups, the authors found that PCM in the co-infected patients progressed more rapidly and also had a higher chance of re-infection than the control group. Based on these results, the authors determined that P. brasiliensis should be considered an AIDS-defining opportunistic pathogen [26].
Authorship
Classification and Introduction by Jocelyn Lotterhos, Organism Key Points by David Li, Daniel Dietrich, Wen Bing Shi, Current Research by Elaina Justiniano-Milby, and Figure 1 by Daniel Dietrich. Edited by Daniel Dietrich, David Li, Wen Bing Shi, Jocelyn Lotterhos, and Elaina Justiniano-Milby students of Dr. Jennifer Bhatnagar in BI311 Microbiology, Boston University.
References
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[2] Negroni, R. Paracoccidiodes brasiliensis (paracoccidiomycosis). Paracoccidiodes brasiliensis (Paracoccidiomycosis)-Infectious Disease and Antimicrobial Agents. (n.d.). http://www.antimicrobe.org/f09.asp
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