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Penicillium marneffei Infection in AIDS  [PDF]
Stephenie Y. N. Wong,K. F. Wong
Pathology Research International , 2011, DOI: 10.4061/2011/764293
Abstract: Penicillium marneffei is a dimorphic fungus which is endemic in Southeast Asia. It is an opportunistic pathogen which has emerged to become an AIDS-defining illness in the endemic areas. Early diagnosis with prompt initiation of treatment is crucial for its management. Prompt diagnosis can often be established through careful cytological and histological examination of clinical specimens although microbiological culture remains the gold standard for its diagnosis. Standard antifungal treatment for AIDS patients with penicilliosis is well established. Highly active antiretroviral therapy should be started early together with the antifungal treatment. Special attention should be paid to potential drug interaction between antiretroviral and antifungal treatments. Secondary prophylaxis may be discontinued with a low risk of relapse of the infection once the immune dysfunction has improved. 1. Introduction Penicillium marneffei was first discovered in 1959 by G. Segretain at the Pasteur Institute in Paris. The strain was isolated from bamboo rats dying of disseminated mycosis in Vietnam. The new species was named P. marneffei in honour of Hubert Marneffe, the Director of Pasteur Institute in Indochina [1, 2]. The first report of human infection due to P. marneffei was also reported by G. Segretain who accidentally pricked his finger with a needle containing the yeast cells of P. marneffei. A small nodule appeared at the site of infection followed by lymphangitis 9 days after the accident [3]. The first natural human infection was reported in 1973 from a patient with Hodgkin lymphoma who lived in Southeast Asia [4]. Before the first case was reported in 1988 in a patient infected with the human immunodeficiency virus (HIV) [5], human penicilliosis was uncommon with less than 40 cases reported in the Southeast Asia [6, 7]. However, the incidence of penicilliosis increased rapidly thereafter with the development of HIV pandemic and the infection became one of the commonest acquired immune deficiency syndrome (AIDS)-defining illnesses among HIV-positive patients in endemic areas [8–10]. 2. Mycology P. marneffei is the only dimorphic fungus in the genus of Penicillium. It exists in mycelial form at 25°C but yeast form at 37°C [1]. It shows a rapid growth rate and matures within 3 days at 25–30°C. Its growth is enhanced in Sabouraud dextrose agar but is inhibited by cycloheximide [11]. At 25°C, the colonies of P. marneffei are granular with shade of greenish-yellow colour and a characteristic red diffusible pigment (Figure 1). Little or no red diffusible pigment
PENICILLIUM MARNEFFEI - AIDS DEFINING ILLNESS  [PDF]
Anaparthy Usharani,M. Bharathi
Our Dermatology Online , 2011,
Abstract: Background: Penicillium marneffei infection is the emerging fungal infection in the present day global scenario of HIV pandemic. P. marneffei is a dimorphic fungi with mycelial growth at 37oC. Suspicion of P.marneffei infection arises when a immunocompromised individuals especially HIV positive persons present with Molluscum contagiosum like skin lesions. But pulmonary manifestations are not characteristic of P.marneffei infection unless we test the sputum for fungal growth in individuals with low CD4 counts ,we may miss P.marneffei respiratory infection. Material and methods: 100 sputum samples from HIV patients with cough were examined for fungal pathogens by inoculating the samples on SDA and incubated at 28oC. The samples with greenish yellow mycelial growth with diffusible red pigment were inoculated on blood agar and SDA and incubates at 37oC for conversion to yeast. Results: We isolated two cases of P.marneffei out of 100 samples. The CD4 counts of the cases were 33 and 84. Conclusions: Early diagnosis and treatment reduces the mortality P.marneffei HIV patients.
Clonality Despite Sex: The Evolution of Host-Associated Sexual Neighborhoods in the Pathogenic Fungus Penicillium marneffei  [PDF]
Daniel A. Henk ,Revital Shahar-Golan,Khuraijam Ranjana Devi,Kylie J. Boyce,Nengyong Zhan,Natalie D. Fedorova,William C. Nierman,Po-Ren Hsueh,Kwok-Yung Yuen,Tran P. M. Sieu,Nguyen Van Kinh,Heiman Wertheim,Stephen G. Baker,Jeremy N. Day,Nongnuch Vanittanakom,Elaine M. Bignell,Alex Andrianopoulos,Matthew C. Fisher
PLOS Pathogens , 2012, DOI: 10.1371/journal.ppat.1002851
Abstract: Molecular genetic approaches typically detect recombination in microbes regardless of assumed asexuality. However, genetic data have shown the AIDS-associated pathogen Penicillium marneffei to have extensive spatial genetic structure at local and regional scales, and although there has been some genetic evidence that a sexual cycle is possible, this haploid fungus is thought to be genetically, as well as morphologically, asexual in nature because of its highly clonal population structure. Here we use comparative genomics, experimental mixed-genotype infections, and population genetic data to elucidate the role of recombination in natural populations of P. marneffei. Genome wide comparisons reveal that all the genes required for meiosis are present in P. marneffei, mating type genes are arranged in a similar manner to that found in other heterothallic fungi, and there is evidence of a putatively meiosis-specific mutational process. Experiments suggest that recombination between isolates of compatible mating types may occur during mammal infection. Population genetic data from 34 isolates from bamboo rats in India, Thailand and Vietnam, and 273 isolates from humans in China, India, Thailand, and Vietnam show that recombination is most likely to occur across spatially and genetically limited distances in natural populations resulting in highly clonal population structure yet sexually reproducing populations. Predicted distributions of three different spatial genetic clusters within P. marneffei overlap with three different bamboo rat host distributions suggesting that recombination within hosts may act to maintain population barriers within P. marneffei.
Protein profiling of the dimorphic, pathogenic fungus, Penicillium marneffei
Julie M Chandler, Erin R Treece, Heather R Trenary, Jessica L Brenneman, Tressa J Flickner, Jonathan L Frommelt, Zaw M Oo, Megan M Patterson, William T Rundle, Olga V Valle, Thomas D Kim, Gary R Walker, Chester R Cooper
Proteome Science , 2008, DOI: 10.1186/1477-5956-6-17
Abstract: Whole cell proteins from the early stages of mould and yeast development in P. marneffei were resolved by two-dimensional gel electrophoresis. Selected proteins were recovered and sequenced by capillary-liquid chromatography-nanospray tandem mass spectrometry. Putative identifications were derived by searching available databases for homologous fungal sequences. Proteins found common to both mould and yeast phases included the signal transduction proteins cyclophilin and a RACK1-like ortholog, as well as those related to general metabolism, energy production, and protection from oxygen radicals. Many of the mould-specific proteins identified possessed similar functions. By comparison, proteins exhibiting increased expression during development of the parasitic yeast phase comprised those involved in heat-shock responses, general metabolism, and cell-wall biosynthesis, as well as a small GTPase that regulates nuclear membrane transport and mitotic processes in fungi. The cognate gene encoding the latter protein, designated RanA, was subsequently cloned and characterized. The P. marneffei RanA protein sequence, which contained the signature motif of Ran-GTPases, exhibited 90% homology to homologous Aspergillus proteins.This study clearly demonstrates the utility of proteomic approaches to studying dimorphism in P. marneffei. Moreover, this strategy complements and extends current genetic methodologies directed towards understanding the molecular mechanisms of phase transition. Finally, the documented increased levels of RanA expression suggest that cellular development in this fungus involves additional signaling mechanisms than have been previously described in P. marneffei.The genus Penicillium is comprised of several hundred species of filamentous fungi (moulds) that are distributed world wide among quite diverse ecosystems [1-3]. The metabolic versatility of species within this taxon has had beneficial, as well as detrimental, impacts upon the environment and othe
In Vivo Yeast Cell Morphogenesis Is Regulated by a p21-Activated Kinase in the Human Pathogen Penicillium marneffei  [PDF]
Kylie J. Boyce,Lena Schreider,Alex Andrianopoulos
PLOS Pathogens , 2009, DOI: 10.1371/journal.ppat.1000678
Abstract: Pathogens have developed diverse strategies to infect their hosts and evade the host defense systems. Many pathogens reside within host phagocytic cells, thus evading much of the host immune system. For dimorphic fungal pathogens which grow in a multicellular hyphal form, a central attribute which facilitates growth inside host cells without rapid killing is the capacity to switch from the hyphal growth form to a unicellular yeast form. Blocking this transition abolishes or severely reduces pathogenicity. Host body temperature (37°C) is the most common inducer of the hyphal to yeast transition in vitro for many dimorphic fungi, and it is often assumed that this is the inducer in vivo. This work describes the identification and analysis of a new pathway involved in sensing the environment inside a host cell by a dimorphic fungal pathogen, Penicillium marneffei. The pakB gene, encoding a p21-activated kinase, defines this pathway and operates independently of known effectors in P. marneffei. Expression of pakB is upregulated in P. marneffei yeast cells isolated from macrophages but absent from in vitro cultured yeast cells produced at 37°C. Deletion of pakB leads to a failure to produce yeast cells inside macrophages but no effect in vitro at 37°C. Loss of pakB also leads to the inappropriate production of yeast cells at 25°C in vitro, and the mechanism underlying this requires the activity of the central regulator of asexual development. The data shows that this new pathway is central to eliciting the appropriate morphogenetic response by the pathogen to the host environment independently of the common temperature signal, thus clearly separating the temperature- and intracellular-dependent signaling systems.
Disseminated Penicillium marneffei infection in a Myanmar refugee from Mizoram state  [cached]
Sood Neelam,Gugnani Harish
Indian Journal of Pathology and Microbiology , 2010,
Abstract: A 30-year-old female, a Myanmar refugee, settled in Mizoram for last three years, reported to our hospital with respiratory symptoms and numerous characteristic skin lesions on multiple sites. Histology and culture of a biopsy from a facial skin lesion established the diagnosis of penicilliosis marneffei. This is first known case of Penicillium marneffei infection from Mizoram state, India to the best of our knowledge. It is possible that several undetected cases of the disease exist in Mizoram, and in the neighboring country, Myanmar and several such cases may be presenting in metropolitan cities.
A p21-Activated Kinase Is Required for Conidial Germination in Penicillium marneffei  [PDF]
Kylie J Boyce,Alex Andrianopoulos
PLOS Pathogens , 2007, DOI: 10.1371/journal.ppat.0030162
Abstract: Asexual spores (conidia) are the infectious propagules of many pathogenic fungi, and the capacity to sense the host environment and trigger conidial germination is a key pathogenicity determinant. Germination of conidia requires the de novo establishment of a polarised growth axis and consequent germ tube extension. The molecular mechanisms that control polarisation during germination are poorly understood. In the dimorphic human pathogenic fungus Penicillium marneffei, conidia germinate to produce one of two cell types that have very different fates in response to an environmental cue. At 25 °C, conidia germinate to produce the saprophytic cell type, septate, multinucleate hyphae that have the capacity to undergo asexual development. At 37 °C, conidia germinate to produce the pathogenic cell type, arthroconidiating hyphae that liberate uninucleate yeast cells. This study shows that the p21-activated kinase pakA is an essential component of the polarity establishment machinery during conidial germination and polarised growth of yeast cells at 37 °C but is not required for germination or polarised growth at 25 °C. Analysis shows that the heterotrimeric G protein α subunit GasC and the CDC42 orthologue CflA lie upstream of PakA for germination at both temperatures, while the Ras orthologue RasA only functions at 25 °C. These findings suggest that although some proteins that regulate the establishment of polarised growth in budding yeast are conserved in filamentous fungi, the circuitry and downstream effectors are differentially regulated to give rise to distinct cell types.
Acute abdomen: An unusual presentation of disseminated Penicillium marneffei infection  [cached]
George I,Sudarsanam T,Pulimood A,Mathews M
Indian Journal of Medical Microbiology , 2008,
Abstract: Varied clinical presentations of Penicillium marneffei , an opportunistic pathogen in HIV disease has been rarely described in literature. We report a patient with advanced AIDS who presented to us with prolonged fever and had features of an acute abdomen. On radiologic imaging he had features of intestinal obstruction and mesenteric lymphadenitis. A diagnosis was made possible by endoscopic biopsies of the small bowel and bone marrow culture which grew P . Marneffei . He was treated with intravenous amphotericin for 2 weeks followed by oral itraconazole. This case is reported for its rarity and unusual presentation and to sensitise clinicians and microbiologists to consider this as an aetiology in patients with advanced HIV/AIDS who present with acute abdomen, more so in patients from a distinct geographic region - South-East Asia
Atypical cutaneous lesions of Penicillium marneffei infection as a manifestation of the immune reconstitution inflammatory syndrome after highly active antiretroviral therapy  [cached]
Saikia Lahari,Nath Reema,Hazarika Debeeka,Mahanta J
Indian Journal of Dermatology, Venereology and Leprology , 2010,
Abstract: Penicillium marneffei infections normally manifest as molluscum contagiosum like skin lesion in HIV-infected persons. We report a case with verrucous lesions over nose and face due to Penicillium marneffei infection after HAART treatment. A 28-year-old man presented, after two weeks of HAART treatment, with multiple erythematous, scaly, papules and nodules with central necrosis predominantly in face and both extremities and scrotum. Microbiological investigations confirmed the diagnosis of Penicillium marneffei infection. This is perhaps the first case report with such manifestation due to Penicillium marneffei infection.
Penicillium marneffei chylous ascites in acquired immune deficiency syndrome: A case report  [cached]
Yin-Zhong Shen,Zhen-Yan Wang,Hong-Zhou Lu
World Journal of Gastroenterology , 2012, DOI: 10.3748/wjg.v18.i37.5312
Abstract: Penicillium marneffei (P. marneffei) infection usually occurs with skin, bone marrow, lung or hepatic involvement. However, no cases of P. marneffei infection with chylous ascites have been reported thus far. In this report, we describe the first case of acquired immune deficiency syndrome (AIDS) which has been complicated by a P. marneffei infection causing chylous ascites. We describe the details of the case, with an emphasis on treatment regimen. This patient was treated with amphotericin B for 3 mo, while receiving concomitant therapy with an efavirenz-containing antiretroviral regimen, but cultures in ascitic fluid were persistently positive for P. marneffei. The infection resolved after treatment with high-dose voriconazole (400 mg every 12 h) for 3 mo. P. marneffei should be considered in the differential diagnosis of chylous ascites in human immunodeficiency virus patients. High-dose voriconazole is an effective, well-tolerated and convenient option for the treatment of systemic infections with P. marneffei in AIDS patients on an efavirenz-containing antiretroviral regimen.
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