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Perennial Ryegrass (Lolium perenne L.).

A protocol that facilitates rapid establishment of Agrobacterium-mediated transformation for perennial ryegrass is described. The synthetic green fluorescent protein (sgfpS65T) reporter gene is introduced in combination with the nptII selectable marker gene into axillary bud derived embryogenic calli of perennial ryegrass (Lolium perenne L.) by co-cultivation with Agrobacterium tumefaciens strain AGL0 harboring binary vector pYF132. Following the co-cultivation calli are cultured for 48 h in liquid callus medium containing timentin at 10 degrees C and 70 rpm, which reduces Agrobacterium overgrowth. Using green fluorescent protein (GFP) as a nondestructive visual marker allows identification of responsive genotypes and transgenic cell clusters at an early stage. GFP screening is combined with paromomycin selection to suppress wild type cells. Transgenic plantlets ready to transfer to soil are obtained within 4 mo of explant culture. Between 8 and 16% of the Agrobacterium-inoculated calli regenerate independent, Southern positive transgenic plants. Reproducibility and efficiency in this perennial ryegrass transformation protocols is controlled by multiple factors including genotype dependent tissue culture and gene transfer response, a short tissue culture-and-selection period and the efficient suppression of Agrobacterium following Agrobacterium-mediated gene transfer.

Agrobacterium tumefaciens↗

Aminoglycoside antibiotics bound to aminoglycoside-detoxifying enzymes and RNA adopt similar conformations.

Conformations of ribostamycin and isepamicin, aminoglycoside antibiotics, bound to an aminoglycoside antibiotic, 3'-phosphotransferase, were determined by transferred nuclear Overhauser effect spectroscopy and molecular modeling. Two major conformers of enzyme-bound ribostamycin, a neomycin-group aminoglyeoside were observed. The 3'- and 5"-OH groups (reactive hydroxyl groups) in the conformers are placed in approximate locations. One of the conformers is similar to the structure of paromomycin bound to a 27-nucleotide piece of ribosomal RNA that represents the A-site of the small ribosomal subunit, where rings A and C are in an orthogonal arrangement. Isepamicin, a kanamycin-group aminoglycoside antibiotic, also showed two major enzyme-bound conformations. Both conformations were similar to those observed for bound isepamicin in the active site of an aminoglycoside(6')-acetyl transferase-Ii. Conformations of other RNA-bound kanamycin-group aminoglycosides were also similar to the enzyme-bound conformations of isepamicin. These observations suggest that aminoglycosides may adopt similar conformations when bound to RNA and protein targets. This may have significant implications in the design of enzyme inhibitors and/or antibiotics.

Animals↗

Treatment of visceral leishmaniasis.

The Leishmania donovani complex includes L. chagasi and L. infantum, and causes visceral leishmaniasis (VL), a disseminated and potentially fatal form of leishmaniasis. The treatment options for VL are limited. Pentavalent antimonials (Sbv) are the first-line treatment options worldwide except for in Europe and Sbv-unresponsive regions of India. Amphotericin B deoxycholate is the drug of choice in India, as are its lipid formulations in Europe. However, liposomal amphotericin B (AmBisome, Gilead Sciences, Inc.) is the best antileishmanial formulation, but its prohibitive cost limits its use in endemic countries. Preferential pricing of AmBisome for patients with VL may provide hope for these underprivileged patients. Oral miltefosine and paromomycin are the other drugs that have been recently developed. Limited therapeutic options, the potential for development of resistance and serious toxicity associated with antileishmanial drugs necessitates a change in the treatment policy. A shift from monotherapy to multi-drug combinations of short courses delivered at no or affordable cost, through directly observed therapy, seems to be the only way to develop the treatment of this disease.

Animals↗

Developments in the treatment of leishmaniasis and trypanosomiasis.

The leishmaniases and trypanosomiases are diseases caused by related parasites belonging to the kinetoplastidae family. They share common biological traits, which are comparatively better known than for other parasites, and which would favour the identification of common targets. Yet, very few new drugs are on the horizon and treatment relies on old, often toxic and ineffective drugs. Miltefosine may soon become the first oral drug registered for Leishmaniasis. Other compounds in clinical trials are paromomycin, sitamquine and lipid formulations of amphotericin B. For African trypanosomiasis old drugs primarily indicated for Chagas disease are being considered (nifurtimox, megazole). Earlier projects are berenil, bisamidines and triazines for African trypanosomiasis, and novel azoles and cruzipain inhibitors for Chagas disease.

Journal Article↗

Efficacy of antigiardial drugs.

The flagellated protozoa Giardia duodenalis is the most commonly detected parasite in the intestinal tract of humans. Infections with the parasite result in diarrhoeal disease in humans and animals, with infants at risk from failure-to-thrive syndrome. The incidence of giardiasis worldwide may be as high as 1000 million cases. Current recommended treatments include the nitroheterocyclic drugs tinidazole, metronidazole and furazolidone, the substituted acridine, quinacrine, and the benzimidazole, albendazole. Paromomycin is also used in some situations, and nitazoxanide is proving to be useful. However, treatment failures have been reported with all of the common antigiardial agents, and drug resistance to all available drugs has been demonstrated in the laboratory. In addition, clinical resistance has been reported, including cases where patients failed both metronidazole and albendazole treatments. The identification of new antigiardial drugs is an important consideration for the future, but maintaining the usefulness of the existing drugs is the most cost-effective measure to ensure the continued availability of antigiardial drugs.

Animals↗

Pharmacokinetic justification of antiprotozoal therapy. A US perspective.

Infections with parasitic protozoa have always been problems for the developing world and are becoming of greater importance to the developed world in this age of easy international travel. The major human protozoal diseases are summarised with an emphasis on their presentation in normal hosts and in immunocompromised individuals and current US drug treatment recommendations are discussed. Present antiprotozoal regimens are based either on a pharmacokinetic rationale or on clinical trial and error. Regimens based on trial and error include amphotericin B against leishmaniasis and arsenic against African trypanosomiasis. Regimens which are to some extent driven by pharmacokinetic or biochemical considerations include paromomycin and metronidazole against amoebiasis, sodium stibogluconate against leishmaniasis, halofantrine and mefloquine against malaria, dihydrofolate reductase (DHFR) inhibitors against Pneumocystis carinii and toxoplasmosis and aerosolised pentamidine against P. carinii pneumonia. The majority of pharmacokinetic studies have been performed only on agents which have some therapeutic activity against other diseases of the developed world. Despite the trend toward rational treatment regimens, no studies have been performed that permit optimisation of antiprotozoal treatment regimens on the basis of clinical conditions such as renal failure.

Antiprotozoal Agents↗

Anthelmintics.

This article describes the drugs used in helminthic infections and their therapeutic indications, mode of action, toxicity and other details of each of the recommended drugs, and discusses the nature and treatment of infection by helminths important in human medicine. Infestation due to the roundworms Enterobius vermicularis, Ascaris lumbricoides and the hookworms, Ancylostoma duodenale and Necator americanus can all be treated effectively with pyrantel pamoate. For Enterobius vermicularis, however, a newer drug, mebendazole, is equally as effective. The advantage of these drugs in the indicated circumstances is that they can be administered in a single dose. Unfortunately, pyrantel pamoate is not a panacea and in the case of Necator it is not as effective as in the other roundworms. In that situation the use of tetrachlorethylene is preferable. For treatment of Strongyloides stercoralis, and important human parasite, because it can become disseminated and lead to fatal infections in immunoincompetent hosts, the only effective drug is thiabendazole. In treatment of Trichuris trichiura infection, mebendazole, administered over a period of 3 days, is the most effective available drug. For the roundworms inhabiting tissues--either as aberrant infections of man or as the normal part of their life cycle in man--therapy tends to be largely non-specific. For example, in visceral larva migrans, caused by the dog roundworm Toxocara canis, only palliative therapy with systemic anti-inflammatory agents and corticosteroids may be helpful. Cutaneous larva migrans, caused by the dog hookworms Ancylostoma brasiliensis and Ancylostoma caninum, is also treated primarily with symptomatic measures, but there is a suggestion that thiabendazole may kill the larvae and thus be effective. Trichinella spiralis may cause severe, even fatal infections in man, but only symptomatic therapy can be offered. Therapy for filarial infections is regrettably complicated and not completely effective. Diethylcarbamazine remains the best available drug, but in some of these infections local surgical excision may also be used. It is important to bear in mind that release of antigens from dying or dead worms may cause systemic inflammatory and allergic reactions that may require therapy with corticosteroids. Therapy for Cestodes is achieved most effectively with niclosamide, but the antimicrobial agent paromomycin has also been effective. For the aberrant cestode infections of man, such as echinococcal cysts or Taenia solium cycticerci, treatment is surgical if the affected areas are accessible. Treatment of schistosomal infections is quite toxic and, therefore, it is mandatory to determine viability of the worms before recommending therapy. If therapy is required, then Schistosoma mansoni infections are treated with stibophen and S. japonicum with antimony potassium tartrate, taking care in both of these instances to watch for the early signs of antimony toxicity; therapy of S. haematobium infections is based on administration of niridazole...

Anthelmintics↗

Practical guide for the treatment of leishmaniasis.

This article summarises the clinical features of visceral, cutaneous and mucocutaneous leishmaniasis, and leishmaniasis in HIV-coinfected patients. The characteristics and clinical use of pentavalent antimonials and the traditional drugs used in all forms of leishmaniasis are described. There have been important developments in therapy, such as aminosidine (paromomycin) conventional amphotericin B and lipid-associated amphotericin B. In most cases of leishmaniasis there is a range of treatment options which is determined by the geographical and clinical features. This review is intended to assist the clinician in choosing treatment and in using unfamiliar drugs with safety and efficacy.

Animals↗

Leishmaniasis: recognition and management with a focus on the immunocompromised patient.

Leishmaniasis is a protozoan disease whose clinical manifestations depend both on the infecting species of Leishmania and the immune response of the host. Transmission of the disease occurs by the bite of a sandfly infected with Leishmania parasites. Infection may be restricted to the skin in cutaneous leishmaniasis (CL), to the mucous membranes in mucosal leishmaniasis or spread internally in visceral leishmaniasis (VL). In the last 2 decades, leishmaniasis, especially VL, has been recognized as an opportunistic disease in immunocompromised patients, particularly those infected with HIV. Leishmaniasis is characterized by a spectrum of disease phenotypes that correspond to the strength of the host's cell-mediated immune response. Both susceptible and resistant phenotypes exist within human populations. Clinical cutaneous disease ranges from a few spontaneously-healing lesions, to diffuse external or internal disease, to severe mucous membrane involvement. Spontaneously-healing lesions are associated with positive antigen-specific T cell responsiveness, diffuse cutaneous and visceral disease with T cell non-responsiveness, and mucocutaneous disease with T cell hyperresponsiveness. Current research is focused on determining the extent to which this spectrum of host response is genetically determined. In endemic areas, diagnosis is often made on clinical grounds alone including: small number of lesions; on exposed areas; present for a number of months; resistant to all types of attempted treatments; and usually no pain or itching. Multiple diagnostic techniques are available. When evaluating treatment, the natural history of leishmaniasis must be considered. Lesions of CL heal spontaneously over 1 month to 3 years, while lesions of mucocutaneous and VL rarely, if ever, heal without treatment. Consequently, all the latter patients require treatment. Therapy is not always essential in localized CL, although the majority of such patients are treated. Patients with lesions on the face or other cosmetically important areas are treated to reduce the size of the resultant scar. In addition, the species of parasite should be identified so that infection with Leishmania braziliensis and Leishmania panamensis can be treated to reduce the risk of development of mucocutaneous disease. Treating patients with Leishmania and HIV co-infection requires close monitoring for effectiveness of treatment, especially because of the high relapse rates. Proven treatments include: antimonials, pentamidine, amphotericin B, interferon with antimony. Treatments where current clinical experience is too limited include: allopurinol, ketoconazole, itraconazole, immunotherapy, rifampin, dapsone, localized heat, paromomycin ointment and cryotherapy. Investigational treatments include: WR6026, liposomal amphotericin and miltefosine. In addition, vaccines for leishmaniasis are being investigated in clinical trials.

HIV Infections↗

Chemotherapy of leishmaniasis.

Leishmaniasis, in its variety of visceral (VL), cutaneous (CL) and mucocutaneous (MCL) forms, directly affects about 2 million people per annum, with approximately 350 million individuals at risk worldwide. During the last 10 years there have been extensive epidemics of the visceral form of the disease, which is also emerging as an important opportunistic infection in immunocompromised patients, especially those co-infected with HIV. The control of leishmaniasis remains a problem principally a zoonotic infection, except in epidemics where it is anthroponotic, interruption of transmission is difficult, though not impossible. No vaccines exist for either VL, CL or MCL and chemotherapy is inadequate and expensive. Current regimes use pentavalent antimony as primary therapy, which must be administered parenterally. Should this fail, a number of other drugs may be employed, depending upon the species of Leishmania concerned and the resources available to the health professionals involved. Recommended secondary treatment employs a variety of drugs, again depending on the nature of the infection. The most widely used of these is amphotericin B, which is highly active but has extensive toxicity complications. The newer formulations of this drug are too expensive to use for the majority of endemic countries. Pentamidine and paromomycin are used in some instances, and a new anti-leishmanial, miltefosine, may be used in the future. In short, there remains a pressing need for new anti-leishmanials and this chapter reviews the current status of chemotherapy, the various avenues being investigated by researchers and their potential application in the future.

Animals↗

Mechanisms of drug action and drug resistance in Leishmania as basis for therapeutic target identification and design of antileishmanial modulators.

The control of Leishmania infections relies primarily on chemotherapy. The arsenal of drugs available against Leishmania infections is limited and includes pentavalent antimonials, pentamidine, amphotericin B, miltefosine, paromomycin, allopurinol, and few other drugs at various stages of their development process. Knowledge about action and resistance mechanisms involved may allow the development of new drugs that minimise or circumvent drug resistance or may identify new targets for drug development. The aim of this review is to propose some chemical topics to design new modulators from the mechanisms of action of drugs and resistance mechanisms to drugs used in the clinic against Leishmania infections. Thus, different classes of ABC transporters extrude antimonials in Leishmania resulting in drug-resistant phenotypes. Compounds interfering with thiol and polyamine metabolism could be designed to inhibit the antimonial detoxication and therefore, such compounds could be used in combination with antimonials. New diamidines could be synthesized in regard to their ability to inhibit topoisomerase II. The challenge for amphotericin B is to be absorbed by oral route requiring labile physico-chemical modifications. New sesquiterpens and flavonoids have to be developed as reversant of antimonial resistance. Although some studies have focused on developing inhibitors against these resistant phenotypes, new efficient modulators that are able to inhibit drug efflux are needed.

ATP-Binding Cassette Transporters↗

Basic studies on ursodeoxycholyl-para-aminobenzoic acid for evaluation of intestinal microflora.

A newly synthesized conjugate of ursodeoxycholic acid with para-aminobenzoic acid (PABA) was investigated to determine its suitability for evaluation of enteric bacteria. This compound, PABA-UDCA, was deconjugated by cholylglycine hydrolase to release free PABA, whereas it was completely resistant to deconjugation by pancreatic and intestinal mucosal enzymes. In bacteriologic experiments almost all the microorganisms that split glycocholic acid deconjugated PABA-UDCA. In rat experiments urinary excretions of PABA were measured during 6 h after oral administration of 10 mg PABA-UDCA (PABA-UDCA administration test). Ten control rats excreted 338.5 +/- 13.8 micrograms (mean +/- SE) of PABA; 10 rats with intestinal stagnant loop excreted more (673.6 +/- 70.2 micrograms; P less than 0.01); whereas 10 rats in each of 7 groups pretreated with oral administration of various antibiotics excreted less (P less than 0.001; polymixin B + tinidazole, 14.0 +/- 2.5 micrograms; polymixin B, 224.9 +/- 23.5 micrograms; tinidazole, 42.7 +/- 8.6 micrograms; kanamycin, 50.3 +/- 5.8 micrograms; clindamycin, 57.4 +/- 7.4 micrograms; vancomycin, 70.4 +/- 8.5 micrograms; and paromomycin, 160.4 +/- 16.4 micrograms). This result was reflected by the bacterial mean count of feces. In the PABA-UDCA administration test, after 2 months of feeding with different diets, rats with high-fiber diet (n = 10) excreted less PABA in urine (70.9 +/- 15.9 micrograms; P less than 0.001) than rats on a control diet (n = 10) and a high-protein-high-fat diet (n = 10) (288.9 +/- 34.5 micrograms and 386.7 +/- 61.2 micrograms, respectively). Fecal bacteriologic status was consistently altered. In human volunteers 250 mg PABA-UDCA was tested. Amounts of PABA excreted in urine during 6 h after dosing were 21.11 +/- 2.02 mg in controls (n = 5) and 12.20 +/- 1.01 mg in the group treated with polymixin B plus tinidazole (n = 5; P less than 0.01). No adverse effect was observed. These basic studies indicate that this compound is likely to offer a simple and rapid method for evaluation of the intestinal microorganisms without use of radioisotopes or expensive, special equipment.

4-Aminobenzoic Acid↗

Antimicrobial susceptibility of bifidobacteria.

The antimicrobial susceptibility of 37 strains of bifidobacteria to 18 antimicrobial agents was determined by a macrodilution broth method. Most of the strains used were isolated from commercial yogurts and starters. Tested organisms were usually sensitive to Gram-positive spectrum antibiotics (bacitracin, erythromycin, lincomycin, and vancomycin), and most of the organisms were inhibited by a concentration < 1.56 micrograms/ml. Erythromycin was the most active agent; all strains were inhibited by < .19 microgram/ml. beta-Lactam antibiotics (penicillin G, ampicillin, methicillin, and cephalothin), showing a wide range of minimum inhibitory concentration, were less effective than Gram-positive spectrum antibiotics. Most strains were somewhat resistant to cephalothin, exhibiting inhibition at concentrations of 6.25 to 25.0 micrograms/ml. Test organisms were most resistant to kanamycin, neomycin, paromomycin sulfate, nalidixic acid, and polymyxin B sulfate; inhibition occurred only at > or = 50 micrograms/ml, and strains were somewhat less resistant to gentamicin and streptomycin. Susceptibility to nitrofurantoin and tetracycline was variable; minimum inhibitory concentrations ranged from 1.56 to 50.0 and .39 to 50.0 micrograms/ml, respectively, but chloramphenicol had a narrow range from 1.56 to 6.25 micrograms/ml.

Aminoglycosides↗

Evaluation of media for selective enumeration of Streptococcus thermophilus, Lactobacillus delbrueckii ssp. bulgaricus, Lactobacillus acidophilus, and bifidobacteria.

Fifteen media were evaluated to determine their suitability for selective enumeration of Streptococcus thermophilus, Lactobacillus delbrueckii ssp. bulgaricus, Lactobacillus acidophilus, and bifidobacteria using 5 to 6 strains of each of the four groups of organisms. Streptococcus thermophilus agar was found to be suitable for selective enumeration of S. thermophilus under aerobic incubation at 37 degrees C for 24 h. The MRS agar at pH 5.2 or reinforced clostridial agar at pH 5.3 could be used for the selective enumeration of L. delbrueckii ssp. bulgaricus when the incubation was carried out at 45 degrees C for > or = 72 h. However, the recovery of this organism was lower on MRS agar at pH 5.2 or reinforced clostridial agar at pH 5.3 than that obtained on MRS agar. The recovery of L. acidophilus and bifidobacteria on MRS agar and MRS-maltose agar was similar; MRS-maltose agar could be used to enumerate total counts of L. acidophilus and bifidobacteria. For selective enumeration of L. acidophilus, MRS-salicin agar or MRS-sorbitol agar could be used. For selective enumeration of bifidobacteria, MRS NNLP (nalidixic acid, neomycin sulfate, lithium chloride, and paromomycin sulfate) agar was suitable; however, determination of bifidobacteria by differential counts between L. acidophilus enumerated on MRS-salicin agar or MRS-sorbitol agar and the total counts of L. acidophilus and bifidobacteria obtained from MRS-maltose agar resulted in higher recovery of some strains of bifidobacteria. Other media that were evaluated in this study were not suitable for selective enumeration.

Bifidobacterium↗

Increase of intestinal Bifidobacterium and suppression of coliform bacteria with short-term yogurt ingestion.

To determine whether ingestion of yogurt would alter human intestinal bacterial composition and whether Bifidobacterium numbers would increase in the intestine, 34 healthy volunteers were studied. The experimental period was 26 d, including an initial 8 d without yogurt, 10 d with three bottles (230 ml each) of AB yogurt per day (President Enterprise Corporation, Tainan, Taiwan), and 8 d without yogurt. Stool samples were taken at 3- to 4-d intervals. The bacteria of each fresh stool sample were promptly analyzed by dilution and culture on blood, MacConkey, Center for Disease Control and NNLP agars, the agar contained nalidixic acid, neomycin sulfate, LiCl, and paromomycin sulfate for aerobes, coliforms, anaerobes, and bifidobacteria, respectively. The number of bacteria was determined as colony-forming units per gram of dried stool. Results indicated that ingestion of AB yogurt increased the counts of anaerobic bacteria, suppressed aerobic bacteria, and significantly elevated the bifidus to coliform ratio. Arbitrarily primed polymerase chain reaction was used to differentiate the identity of bifidobacteria in four volunteers before and after yogurt ingestion and confirmed that B. bifidum ingested from the yogurt survived and proliferated in the stool throughout the experiment. However, the elevated bifidus to coliform ratio gradually diminished and disappeared after yogurt consumption was discontinued. In conclusion, ingestion of yogurt increased the numbers of stool bifidobacteria and suppressed coliform bacteria. The ingested bifidobacteria survived for more than 8 d after yogurt consumption was discontinued.

Adult↗

Antiparasitic agents.

Several important developments have occurred in recent years in the chemotherapy for and prophylaxis of parasitic infections. Although mefloquine is clearly the most effective agent for prevention of chloroquine-resistant falciparum malaria, its use has been compromised by side effects, both real and imagined. Well-designed studies have shown that side effects occur no more frequently with low-dose mefloquine than with chloroquine. Use of mefloquine in pregnant women has not been associated with birth defects, but the incidence of stillbirths may be increased. Malarone is a new agent that combines atovaquone and proguanil, and it may be as effective as mefloquine; however, it is not yet available in the United States. Several newer agents have appeared in response to the development of multidrug resistant Plasmodium falciparum, especially in Southeast Asia. Halofantrine is available for the treatment of mild to moderate malaria due to P. falciparum and for P. vivax infections. Because of severe toxic effects, use of halofantrine should be restricted to only those unusual and rare situations in which other agents cannot be used. Artemisinin (an extract of the Chinese herbal remedy qinghaosu) and two derivatives, artesunate and artemether, are active against multidrug resistant P. falciparum and are widely used in Asia in oral, parenteral, and rectal forms. The antibacterial azithromycin in combination with atovaquone or quinine has now been reported to treat babesiosis effectively in experimental animals and in a few patients. Azithromycin in combination with paromomycin has also shown promise in the treatment of cryptosporidiosis (and toxoplasmosis when combined with pyrimethamine) in patients with the acquired immunodeficiency syndrome (AIDS). Albendazole is currently the only systemic agent available for treatment of microsporidiosis, an infection primarily of patients with AIDS. In addition, albendazole and ivermectin have emerged as effective broad-spectrum antihelminthics, with albendazole becoming the drug of choice for hydatid disease (echinococcosis), neurocysticercosis, and most intestinal nematode infections (except strongyloidiasis and trichuriasis). Liposomal amphotericin B is the first drug approved by the Food and Drug Administration for the treatment of visceral leishmaniasis.

Antiparasitic Agents↗

Mutational biosynthesis of a new antibiotic, streptomutin A, by an idiotroph of Streptomyces griseus.

Microorganisms producing antibiotics have been genetically converted by earlier workers to mutants which cannot produce antibiotic without supplementation with a moiety of the antibiotic. These antibiotics include neomycin, kanamycin, paromomycin, butirosin, sisomicin, ribostamycin and novobiocin. Success has not been reported for organisms producing guanidinocyclitol antibiotics such as streptomycin. We mutagenized conidia of the streptomycin-producing Streptomyces griseus strain 7-455F3 with nitrosoguanidine at pH 7.0. Non-producers of streptomycin were visually selected by the agar-plug technique using Bacillus subtilis. We successfully isolated mutant MIT-A5 which produces no streptomycin unless streptidine is added to the agar medium. The streptidine-dependent phenotype was confirmed in submerged culture in flasks. Attempts to produce new antibiotics by feeding aminocyclitols to mutant MIT-A5 failed. However a new antibiotic (streptomutin A) was produced by supplementation with the guanidinocyclitol, 2-deoxystreptidine. We propose the term "mutational biosynthesis" for the production of new metabolites by the use of mutants blocked in the biosynthetic pathway to the secondary metabolite. We further propose the term "idiotroph" to properly describe such mutants.

Anti-Bacterial Agents↗

Interspecific recombination among aminoglycoside producing streptomycetes.

From auxotrophic double mutants of Streptomyces rimosus forma paromomycinus and Streptomyces kanamycerticus producing little or no antibiotic, stable prototrophic recombinants were obtained with low frequencies. Most of the recombinants differed from the parents in morphology and antibiotic production. The most frequent classes of recombinants behaved as streptomycetes of the "red" series and produced a wide range of neomycin yields, in contrast to the parents which produced paromomycin and a small proportion of neomycin, or kanamycin, respectively. Hypotheses on the nature of the genetic material exchanged are discussed.

Aminoglycosides↗