J.M. Mata

Bio: J.M. Mata is an academic researcher. The author has contributed to research in topics: Fosfomycin & Respiratory tract infections. The author has an hindex of 4, co-authored 4 publications receiving 605 citations.

Phosphonomycin, a New Antibiotic Produced by Strains of Streptomyces

Abstract: Phosphonomycin is a newly discovered antibiotic produced by streptomycetes. It is effective, when administered by the oral route, to mice infected with Gram-positive or Gram-negative microorganisms. The antibiotic is bactericidal and inhibits cell-wall synthesis.

Fosfomycin: Laboratory studies.

Abstract: Fosfomycin, a nontoxic broad-spectrum antibiotic, different in structure from all previously described antibiotics, acts selectively by inhibiting cell wall formation. It was overlooked during many years of screening because of antagonism by culture medium ingredients and frequent occurrence of resistant mutants. It is effective in many because the neutralizing substances are not present and resistant mutants of most species are avirulent. Fosfomycin has favorable pharmacologic characteristics. It is not cross resistant, does not show antagonism, and has been used successfully in combinations. An insoluble calcium salt is used in oral formulation and a sodium salt for parenteral administration. Overall success rates of 86% were reported with 1,000 patients in Spain and 79% in Japan.

Bacteriological evaluation of fosfomycin in clinical studies.

Abstract: Since fosfomycin has behaved in vitro as a broad-spectrum antibiotic, an attempt has been made to evaluate this behaviour in controlled clinical study carried out at different Spani

Challenges of Antibacterial Discovery

Abstract: Summary: The discovery of novel small-molecule antibacterial drugs has been stalled for many years. The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort. The major challenges fall into two areas: (i) proper target selection, particularly the necessity of pursuing molecular targets that are not prone to rapid resistance development, and (ii) improvement of chemical libraries to overcome limitations of diversity, especially that which is necessary to overcome barriers to bacterial entry and proclivity to be effluxed, especially in Gram-negative organisms. Failure to address these problems has led to a great deal of misdirected effort.

The mechanism of action of fosfomycin (phosphonomycin)

Abstract: The discovery of fosfomycin, a new antibiotic produced by strains of Streptomyces, was announced under its former name phosphonomycin by Hendlin and colleagues in 1969.l The chemical structure shown in FIGURE 1 combines two unusual features: an epoxide ring, rare among antibiotics, and a carbon-phosphorus bond which is seen to occur here for the first time among the natural products of the bacteria. Most of the present account concerns the determination of the enzymatic step in cell wall biosynthesis that is ultimately blocked by fosfomycin. We compare in detail the action of that enzyme’s catalytic center upon the antibiotic and its normal substrate. We also describe the role of two stereospecific nutrient transport systems that by mediating the entry and accumulation of fosfomycin comprise the determining factors in the sensitivity of various bacteria to this polar antibiotic. Although the main conclusions of these mechanism of action studies were briefly stated by us in the initial announcement,’, the present publication is the first in which there appears any portion of the original experimental data that support those conclusions. Several reports have appeared from other laboratories 4, and from our own IJ in which certain basic findings and methodology were reproduced in the course of pursuing the independent goals of their studies. Their additional contributions to the understanding of fosfomycin action are cited at appropriate points in the succeeding text.

Natural product discovery: past, present, and future

Abstract: Microorganisms have provided abundant sources of natural products which have been developed as commercial products for human medicine, animal health, and plant crop protection. In the early years of natural product discovery from microorganisms (The Golden Age), new antibiotics were found with relative ease from low-throughput fermentation and whole cell screening methods. Later, molecular genetic and medicinal chemistry approaches were applied to modify and improve the activities of important chemical scaffolds, and more sophisticated screening methods were directed at target disease states. In the 1990s, the pharmaceutical industry moved to high-throughput screening of synthetic chemical libraries against many potential therapeutic targets, including new targets identified from the human genome sequencing project, largely to the exclusion of natural products, and discovery rates dropped dramatically. Nonetheless, natural products continued to provide key scaffolds for drug development. In the current millennium, it was discovered from genome sequencing that microbes with large genomes have the capacity to produce about ten times as many secondary metabolites as was previously recognized. Indeed, the most gifted actinomycetes have the capacity to produce around 30-50 secondary metabolites. With the precipitous drop in cost for genome sequencing, it is now feasible to sequence thousands of actinomycete genomes to identify the "biosynthetic dark matter" as sources for the discovery of new and novel secondary metabolites. Advances in bioinformatics, mass spectrometry, proteomics, transcriptomics, metabolomics and gene expression are driving the new field of microbial genome mining for applications in natural product discovery and development.

Natural products and drug discovery. Can thousands of years of ancient medical knowledge lead us to new and powerful drug combinations in the fight against cancer and dementia

Abstract: The medicinal use of natural products—compounds that are derived from natural sources such as plants, animals or micro‐organisms—precedes recorded human history probably by thousands of years. Palaeoanthropological studies at the cave site of Shanidar, located in the Zagros Mountains of Kurdistan in Iraq, have suggested that more than 60,000 years ago, Neanderthals might have been aware of the medicinal properties of various plants, as evidenced by pollen deposits in one of the graves at the site (Solecki, 1975). Over the ensuing millennia, humankind discovered and made use of an enormous range of natural compounds; the latest version of the Dictionary of Natural Products (DNP; http://dnp.chemnetbase.com) has just over 214,000 entries. Throughout our evolution, the importance of natural products for medicine and health has been enormous. Since our earliest ancestors chewed on certain herbs to relieve pain, or wrapped leaves around wounds to improve healing, natural products have often been the sole means to treat diseases and injuries. In fact, it has only been during the past decades that natural products have taken a secondary role in drug discovery and drug development, after the advent of molecular biology and combinatorial chemistry made possible the rational design of chemical compounds to target specific molecules. The past few years, however, have seen a renewed interest in the use of natural compounds and, more importantly, their role as a basis for drug development. The modern tools of chemistry and biology—in particular, the various ‘‐omics’ technologies—now allow scientists to detail the exact nature of the biological effects of natural compounds on the human body, as well as to uncover possible synergies, which holds much promise for the development of new therapies against many devastating diseases, including dementia and cancer. > …Throughout our evolution, the importance of natural products for medicine and health has been enormous Owing …

Pharmaceutically active secondary metabolites of microorganisms.

Abstract: The antibiotics have been useful in our battles against infectious bacteria and fungi for over 50 years. However, many antibiotics are used commercially, or are potentially useful, in medicine for activities other than their antibiotic action. They are used as antitumor agents, immunosuppressive agents, hypocholesterolemic agents, enzyme inhibitors, antimigraine agents, and antiparasitic agents. A number of these products were first discovered as antibiotics which failed in their development as such, or as mycotoxins. In addition to the above alternative applications, new powerful antibiotics have been discovered and commercialized in recent years and others are in clinical testing at the moment. A few successful secondary metabolites appear to have no antibiotic activity. The recently increased development of resistance to older antibacterial and antifungal drugs is being met with the use or clinical testing of older, underutilized or previously nondeveloped narrow-spectrum antibacterial products as well as powerful semisynthetic antifungal agents.