Exploring host-pathogen interactions in the Dictyostelium discoideum-Mycobacterium marinum infection model of tuberculosis.

Mycobacterium tuberculosis is a pathogenic mycobacterium that causes tuberculosis. Tuberculosis is a significant global health concern that poses numerous clinical challenges, particularly in terms of finding effective treatments for patients. Throughout evolution, host immune cells have developed cell-autonomous defence strategies to restrain and eliminate mycobacteria. Concurrently, mycobacteria have evolved an array of virulence factors to counteract these host defences, resulting in a dynamic interaction between host and pathogen. Here, we review recent findings, including those arising from the use of the amoeba Dictyostelium discoideum as a model to investigate key mycobacterial infection pathways. D. discoideum serves as a scalable and genetically tractable model for human phagocytes, providing valuable insights into the intricate mechanisms of host-pathogen interactions. We also highlight certain similarities between M. tuberculosis and Mycobacterium marinum, and the use of M. marinum to more safely investigate mycobacteria in D. discoideum.

The loss of the PDIM/PGL virulence lipids causes differential secretion of ESX-1 substrates in Mycobacterium marinum.

The mycobacterial cell envelope is a major virulence determinant in pathogenic mycobacteria. Specific outer lipids play roles in pathogenesis, modulating the immune system and promoting the secretion of virulence factors. ESX-1 (ESAT-6 system-1) is a conserved protein secretion system required for mycobacterial pathogenesis. Previous studies revealed that mycobacterial strains lacking the outer lipid PDIM have impaired ESX-1 function during laboratory growth and infection. The mechanisms underlying changes in ESX-1 function are unknown. We used a proteo-genetic approach to measure phthiocerol dimycocerosate (PDIM)- and phenolic glycolipid (PGL)-dependent protein secretion in M. marinum, a non-tubercular mycobacterial pathogen that causes tuberculosis-like disease in ectothermic animals. Importantly, M. marinum is a well-established model for mycobacterial pathogenesis. Our findings showed that M. marinum strains without PDIM and PGL showed specific, significant reductions in protein secretion compared to the WT and complemented strains. We recently established a hierarchy for the secretion of ESX-1 substrates in four (I-IV) groups. Loss of PDIM differentially impacted secretion of Group III and IV ESX-1 substrates, which are likely the effectors of pathogenesis. Our data suggest that the altered secretion of specific ESX-1 substrates is responsible for the observed ESX-1-related effects in PDIM-deficient strains.IMPORTANCEMycobacterium tuberculosis, the cause of human tuberculosis, killed an estimated 1.3 million people in 2022. Non-tubercular mycobacterial species cause acute and chronic human infections. Understanding how these bacteria cause disease is critical. Lipids in the cell envelope are essential for mycobacteria to interact with the host and promote disease. Strains lacking outer lipids are attenuated for infection, but the reasons are unclear. Our research aims to identify a mechanism for attenuation of mycobacterial strains without the PDIM and PGL outer lipids in M. marinum. These findings will enhance our understanding of the importance of lipids in pathogenesis and how these lipids contribute to other established virulence mechanisms.

Infección cutánea por Mycobacterium marinum / Skin infection due to Mycobacterium marinum

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Mycobacterium marinum como agente productor de lesiones dermatológicas: a propósito de 2 casos / Mycobacterium marinum as a causative agent of skin lesions: report of 2 cases

El artículo recoge de una manera descriptiva y didáctica los aspectos etiopatogénicos más importantes de Mycobacterium marinum como agente productor de lesiones dermatológicas, mediante la descripción de 2 casos ocurridos en el Hospital de Mérida. Así mismo, se describen tanto la actitud diagnóstica, como el diagnóstico diferencial, las lesiones y el tratamiento de esta microbacteria con el fin de procesar y manejar mejor los futuros casos que se lleguen a presentar (AU)

This article presents a descriptive and instructive review of the most important a etiological and pathogenic features of Mycobacterium marinum as a causative agent of dermatological lesions, using the reporting of two cases occurring in the Hospital de Merida. The differential diagnosis, lesions and treatment of these types of infections are also discussed, so that future cases may be diagnosed earlier and treated appropriately (AU)

Acute infection due to Mycobacterium marinum in a patient with ulcerative colitis and metabolic syndrome on infliximab therapy / Infección aguda por Mycobacterium marinum en un paciente con colitis ulcerosa y síndrome metabólico bajo tratamiento con infliximab

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Infección cutánea por Mycobacterium marinum / Skin infection by Mycobacterium marinum

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Infección por Mycobacterium marinum. Características epidemiológicas, clínicas y tratamiento / Mycobacterium marinum skin infections. Epidemiology, clinical features and treatment

El Mycobacterium marinum (MM) es una micobacteria atípica que afecta a diferentes especies de peces. La infección en el humano se produce por elcontacto directo con peces o con aguas contaminadas. Es un problema emergente relacionado al pasatiempo del cuidado de peceras. En este trabajo se informan ocho casos de infección cutánea por MM ocurridos entre 1990 y 2007 en dos centros de la Argentina, incluyendo una forma atípica de presentación clínica no publicada en la bibliografía consultada (AU)

Mycobacterium marinum (MM) is an atypical mycobacteria. MM can affect different fish species. Humans can be infected by direct contact with fish or contaminated water. Mycobacterium Marinum infections are an emerging problem related to “fish tank hobby”.Eight cases of cutaneous infection with Mycobacterium marinum were studied in two medical center in Argentina from 1990 to 2007. We describean atypical clinical presentation, to our knowledge not previously reported (AU)

Infecciones cutáneas y de partes blandas por micobacterias no tuberculosas / Cutaneous and soft skin infections due to non-tuberculous mycobacteria

En los últimos años se ha observado un aumento en el número de aislamientos y variedad de especies de micobacterias no tuberculosas (MNT). Aunque la totalidad de las MNT patógenas pueden causar infecciones cutáneas y de tejidos blandos, las más frecuentes son las de crecimiento rápido (Mycobacterium fortuitum, Mycobacterium chelonae y Mycobacterium abscessus), Mycobacterium marinum y Mycobacterium ulcerans. La mayoría de las micobacteriosis cutáneas están causadas por especies de distribución mundial, como las micobacterias de crecimiento rápido, M. marinum, complejo Mycobacterium avium, Mycobacterium kansasii o Mycobacterium xenopi. Sin embargo, otras tienen una delimitación geográfica, como M. ulcerans, que produce una infección cutánea endémica, sobre todo en África central y occidental (úlcera de Buruli) y Australia (úlcera de Bairnsdale), donde es la tercera enfermedad micobacteriana más frecuente tras la tuberculosis y la lepra. Las micobacteriosis cutáneas suelen producirse por la exposición de heridas traumáticas o quirúrgicas al agua o productos contaminados con MNT, o bien por una enfermedad diseminada, mayormente, en los pacientes inmunodeprimidos. Para el diagnóstico, es necesario un elevado grado de sospecha ante lesiones cutáneas crónicas en pacientes con antecedentes de heridas cutáneas y exposición de riesgo, y con estudios microbiológicos convencionales negativos. En la mayoría de las MNT no se suele recomendar las pruebas de sensibilidad convencionales a los fármacos, salvo en ciertas especies, o en caso de fracaso terapéutico. El tratamiento se basará en la combinación de diversos antimicrobianos, teniendo en cuenta que las MNT presentan una mayor resistencia a los antituberculosos convencionales. En los casos graves y con afectación de tejidos o estructuras profundas se deberá recurrir al tratamiento quirúrgico

The frequency of isolation as well as the number of species of non-tuberculous mycobacteria (NTM) has increased in the last years. Nearly every pathogenic species of NTM may cause skin and soft tissue infections, but rapidly growing mycobacteria (Mycobacterium fortuitum, Mycobacterium chelonae and Mycobacterium abscessus), Mycobacterium marinum and Mycobacterium ulcerans are the most commonly involved. Many of these cutaneous mycobacteriosis, such as rapidly growing mycobacteria, M. marinum, Mycobacterium avium complex, Mycobacterium kansasii or Mycobacterium xenopi are world-wide distributed. In contrast, some others have a specific geographical distribution. This is the case of M. ulcerans, which causes a cutaneous diseases endemic of Central and West Africa (Buruli ulcer) and Australia (Bairnsdale ulcer), being the third mycobacterial infection after tuberculosis and leprosy. Cutaneous mycobacteriosis usually appear either after contact of traumatic or surgical wounds with water or other contaminated products, or, secondarily, as a consequence of a disseminated mycobacterial disease, especially among immunosuppressed patients. For an early diagnosis, it is necessary to maintain a high degree of suspicion in patients with chronic cutaneous diseases and a history of trauma, risk exposure and negative results of conventional microbiological studies. In general, individualized susceptibility testing is not recommended for most NTM infections, except for some species, and in case of therapeutic failure. Treatment includes a combination of different antimicrobial agents, but it must be taken into account that NTM are resistant to conventional antituberculous drugs. Severe cases or those with deep tissues involvement could also be tributary of surgical resection

Nódulo eritematoso en el dorso de la mano / Erythematous nodule on the back of the hand

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Granuloma de los acuarios: presentación de tres casos / Aquarium granuloma: presentation of three cases

El granuloma de los acuarios es una afección crónica causada por una micobacteria atípica de crecimiento lento, identificada como Mycobacterium marinum. Este germen cuyo hábitat natural es el agua, sólo es patógeno para la piel escoriada. Se presenta el cuadro clínico e histopatológico característico de tres casos evaluados en nuestro medio, con la identificación microbiológica del germen, y respuesta favorable al tratamiento establecido