World-wide the majority of actinomycetoma cases as mention above can be caused by Streptomyces somaliensis, Actinomadura madurae; Actinomadura pelletieri, Nocardia (N. brasiliensis; N. asteroides; N. otitidis-caviarum; N. transvalensis), and new species of the genus Nocardia: N. harenae and N takedensis [10] However molecular identification of reference collections has demonstrated that misidentifications were common and currently the true species distribution over the world is not known [10, 11]. In this communication, we report on the first case of human actinomycetoma infection caused by a yellow-grain-producing bacteria Micromonospora olivasterospora. We identified the causative agent by molecular and taxonomy techniques. Our strain was clustered in the Actinomycetota order Micromonosporales a member of Micromonosporaceae family and it encompasses more than 105 species (https://lpsn.dsmz.de/genus/ micromonospora), including the recent identify species Micromonospora orduensis [27], Micromonospora deserti [28], Micromonospora craterilacus [29] and Micromonospora pelagivivens [30] .
The genus micromonospora are a group of rare actinomycetes which scattered worldwide, and most of the species colonize plant debris, water, deep marine sediments, sandstone, insects, and soil [22–27], with a single isolate of Micromonospora sp. was recovered from a case of pneumonia of unknown etiology from Nigeria [31].
It was firstly described by Ørskov (1923) as a member of the family Micromonosporaceae with Micromonospora chalcea as its type species [26]. All members of the genus are Gram-positive, aerobic, non-motile actinobacteria that own unique morphological characteristics such as single spore attached to short substrate hyphae.
Colonial morphology, along with microscopic examination of mycelia, spore characteristics and growth requirements, provide useful clues to the genus level identification of actinomycetes [13]. Physiological and biochemical characteristics, providing clues as to identification of the microorganisms for phenotypic characterization [32, 33].
Our isolates were identified as strains of the genus Micromonospora on the basis of colony morphology and molecular taxonomy. Maximum sodium chloride tolerance is a very important physiological characteristic of the genus Micromonospora as this is the character that most readily differentiates strains into groups. The diagnostic mycelial pigment colour, as well as diffusible pigment colour, are also very significant characters. In general, the pigments of their mycelia are in orange, red, green or brown color. Soluble pigments are produced by Micromonospora chalcea (yellow), Micromonospora halophytica (red-brown), Micromonospora olivasterospora (olive-green), Micromonospora purpureochromogenes (dark-brown), and Micromonospora rosaria (wine-red) [32]. Micromonospora coerulea (blue-green) and Micromonospora echinospora (maroon-purple) produced pigments sensitive to pH changes [32].
Further investigation using sequencing-based approaches is required to identify actinomycetes at species level accurately and evaluate antibiotic resistance patterns in order to prevent the progression of infection.
TMP-SMX is the first-line antibacterial agent for years in initial therapy of actinomycetes, nocardiosis, Streptomyces and actinomycetoma infection, occasionally combines with amikacin, third-generation cephalosporins, linezolid or imipenem [34–36]. Therefore accurate determination of the susceptibility to TMP-SMX in clinical isolates is crucial. However, sulfonamide-resistant or linezolid-resistant strains have been isolated in clinical in recent years, which brings great challenges to the clinical treatment of actinomycetes in general [37, 38].In addition, sulfonamides are of great toxicity and side effects [39–42] .Because of the limited number of studies reporting antibiotic susceptibility profiles of actinomycetoma causative agents [43], with respect to the total of Over 700 species of Streptomyces bacteria have been described, more than 40 known species of Actinomyces species names validly published and the genus Nocardia contains 80–100 species, in addition to Micromonospora species ; antibiotic therapy against such infections is at best questionable. There is a consistent agreement that clinical actinomycetoma isolates are susceptible to amikacin, gentamycin, vancomycin, and linezolid. In contrast, the vast majority of clinical isolates tested to date have been resistant to penicillin. The results available in the literature suggest species-specific susceptibility, for this reason, antimicrobial sensitivity test, sulfonamide-resistant genes (sulf1-sulf2, int1-int3), trimethoprim-resistant gene (DfrA)and amikacin resistance gene (rrs ) were carried out for our isolate and our patient received amikacin sulfate (15 mg/kg twice daily for 5 weeks), folic acid 5 mg once per day and co-trimoxazole (960 mg twice daily for 6 weeks); Our patient responded well to treatment as the sinuses started to heal and the lesions decreased in size in the several months of treatment he received.
In conclusion, we reported on the first human actinomycetoma caused by Micromonospora olivasterospora to the list of bacteria causing human yellow grain actinomycetoma. The treatment of actinomycetoma causative agents depends on the identification of the strain and the results of drug sensitivity.