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Global Indoor Health Network 

Streptomyces

Streptomyces
Streptomyces is the largest genus of the Actinobacteria with over 500 known species, belonging to the family Streptomycetaceae. They are found predominantly in soil and decaying vegetation. They are gram positive and have a mycelium-type growth resembling molds. The DNA has a high G-C content. 

Most Streptomyces produce spores, and they are noted for the “earthy” odor following a rain because of the production of the volatile compound geosmin. 

Streptomyces is the largest antibiotic producing genus in the microbial world. The estimated number of secondary antimicrobial compounds produced by this genus is estimated to be about 100,000. These include antifungals, antibiotics and chemotherapeutic chemicals. 

Search of the National Library of Medicine via entrez pubmed gave a list of 7,683 published research papers on the subject of Streptomyces + antibiotics. The identification and production of antimicrobial compounds produced by this genus began in the 1970s and continues to current. The antimicrobial compounds currently or formerly in use will be briefly reviewed below. 

Following this review, the presence of various species of Streptomyces in damp indoor spaces will be discussed.

Antifungals from Streptomyces species 

Streptomyces produce numerous antifungal compounds which belong to the polyene antimycotics. Polyene antimycotics, sometimes referred to as polyene antibiotics, are a class of antimicrobial compounds targeting molds. 

The polyenes bind to ergosterol in the fungal cell membrane and promote leakiness which may contribute to fungal cell death. Their chemical structural feature is a large ring of atoms (essentially a cyclic ester ring) containing multiple conjugated carbon-carbon double bonds (hence polyene) on one side of the ring and multiple hydroxl groups bonded to the other side of the ring. Their structures often have a d-mycosamine (a type of amino-glycoside) group bonded to the molecule. 

The series of conjugated double bonds typically absorbs strongly in the ultraviolet-visible region of the electromagnetic spectrum, often resulting in the polyene antibiotics having a yellow color.

Examples of polyene antifungals are Nystatin (S. noursei), Amphotericin B (S. nodosus) and Natamycin (S. natlensis).

Antibiotics from Streptomyces species

Streptomyces species are the source of a large number of antibiotics. As mentioned above, over 7500 research papers have been published on this subject. The most frequently used and medically important antibiotics are:

Eryrthromycin (S. fradiae) 

Neomycin (S. griseus) 

Streptomycin (S. rimosus)

Tetracycline (S. Rimosus) 

Vancomycin (S. Orientals)

Daptomycin (S. Rosesporus)

Rifamycin (S. mediterranei) 

Chloramphenicol (S. venezuelae)

Puromycin (S. alboniger)

Lincomycin (S. lincolnensis) 

Cefoxin (S. lactamdurans)

Chemotherapeutic Chemicals from Streptomyces species

Anthracyclines were the subject of cancer treatment since the 1970s. The daunosamine and tetra-hydronaphthacenedione-based compounds are cell-cycle nonspecific and are used to treat a large number of cancers including lymphomas and leukemia and uterine, ovarian, lung and breast cancers. 

Anthracyclines drugs are developed from natural resources. 

Daunorubicin was discovered by isolating it from soil-dwelling fungus Streptomyres. 

Doxorubicini which is another commonly used anthracycline chemotherapy agent, is isolated from mutated strain of Streptomyces. 

Although both the drugs have similar mechanisms, doxorubicin is more effective in treating solid tumors, Idarubicinf Epirubicin, and Mitoxantrone are other commonly used anthracycline chemotherapy drugs. 

Anthracyclines work by forming free radicals that break DNA strands thereby inhibiting DNA synthesis and function. These chemotherapeutic agents form a complex with DNA and enzyme to inhibit the topoisomerase enzyme. Topoisomerases are enzymes that causes the supercoiling of DNA, allowing DNA repair, transcription and replication. 

Cardiac toxicity is a serious side effect of anthracyclines as heart muscle can be damaged. The various chemotherapeutic compounds are produced by the following Streptornyces Streptomyces gtiseus, var. rubidofaciens (Daunorubkn), Streptomyces peucetius (doxorubkin) and Streptomyces iividans TK24 (produces daunomycin to doxorubicin). 
Streptomyces slides

Streptomyces slides


Streptomyces Identified in Damp Indoor Spaces 

The number of bacteria in the indoor air are frequently higher than mold spores. Thus, several studies have reported the identification of both Gram positive and Gram negative bacteria in indoor environments, Actinobacteria and, in particular, Streptomyces species, are present in the indoor environments. 

The identification of these organisms is briefly discussed below. 

The Gram-positive bacteria isolated from water-damaged building materials include species of Arthrobacter, Bacillus, Gondona, Micrococcus., Mycobactetiurn, Paenibacillus and Streptomyces (see Peltola, et a1,1001; Anderson et al, 1997). 

The Streptomyces present in water-damaged building materials are diverse and include strains of the following species: iividans, anuiatus, diastatirus, aibidofiavusi virginiae and thermovulgaris (Pietarinen et al, 2008; Rintala et al, 2002). 

Of the Streptomyces species, S. californicus has been shown to produce toxins that are very potent inducers of inflammatory cytokines in vitro and in a mouse model. 

Streptomyces species produce the toxin, Valinomycin, which is a mitochondrial toxin and induces an inflammatory response in vitro. Moreover, Rintala et al, 2004 described the presence of Streptomyces species in house dust of water-damaged homes. 

The four species, albidoflavus, virginiae, annula us, halstedii, and diastaticus were more plentiful than in undamaged homes.

In addition, the authors reviewed the literature on the subject of indoor bacteria. The review cited literature that identified Streptomyces, other Actinobacteria, as well as negative bacteria in these environments. 

Health Effects of Streptomyces and Thermo Actinomycetes 

Streptomyces species are considered as saprophytic bacteria present in soil and decaying organic matter. However, they are found in water-damaged buildings where the occupants have become ill. The genus is considered an opportunistic pathogen causing infection. 

Streptomyces can cause the formation of mycetoma. Mycetoma are granulomatous lesions of the skin but also can be systemic (Martin et al, 2004; Develoux etal, 1988; Develoux et al, 1995). They are most common in tropical environments. 

Infections have been reported in both immune-compromised and immune-competent patients. The identified species are maritmus, olivadeus, albus, nobilis, parvulus, humidus, pilosus, indigofetus and herbaricolor. 

The infections include septicemia, pneumonia, brain abscess, peritonitis, pericarditis, endocarditis, knee, lung abscess and intraveneous catheters (Kapadia, et al, 2007). A brain abscess following skull penetration trauma has been reported along with isolates of additional Actinobacteria (Rose et al, 2008). 

Other cases reported in the literature are neonatal infection (Werder et al, 1973), septicemia with thrombosis (Carey et al, 2001; Ghanem et al, 2007) and silicone breast implant (Manteca et al, 2009).

Streptomyces infections can lead to the development of mycetoma.

Lung Disease Associated Mesophilic and Thermo Actinomycetes

Thermophilic Actinomycetes are cultured at an optimum temperature of 55 oC. Therefore, they are missed at culture temperature done at 37 oC by microbiology laboratories.

In addition, these bacteria are slow growing and are missed because cultures are not maintained for a sufficient period of time.

Hypersensitivity pneumonitis (HP) or extrinsic allergic alveolitis is a complex syndrome that has three types of conditions: acute (lasts 3-4 days), subacute (intermittent) and chronic. It is characterized by diffuse inflammation of the airways with noncaseating interstitial granulomas and mononuclear cell infilatration and may have centrilobular fibrosis.

The common names associated with HP are Farmer's Lung Disease, Grain Handler's Lungs, Humidifier/Airconditioner lung, Bird Breeder's Lung, Cheese worker's lung, Bagassosis and Malt worker's lung. The precipitating agent is an immune response to microbial antigens or molds and bacteria.

The bacteria identified to cause this condition in damp indoor spaces includes Streptomyces spp. and Thermoactinomyces spp. (Kampfer et al, 2005; Fenoglio et al, 2007; Roussel et al, 2005; Che et al, 1989; Kagen et al, 1981; Roberts et al, 1983; Hollingdale, 1975).
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