| Recent
Patents on Anti-Infective Drug Discovery
ISSN: 1574-891X
Recent Patents on Anti-Infective
Drug Discovery
Volume 4, Number 2, June 2009
Contents
Novel Antibiotic Compounds Produced by the Insect Pathogenic
Bacterium Photorhabdus Pp. 81-89
Ioannis G. Eleftherianos
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Hybolites: Novel Therapeutic Tools for
Targeting Hyperstructures in Bacteria Pp. 90-95
Guillaume Legent and Victor Norris
[Abstract] [Purchase
Issue/Articles]
Chemical Structure and Biological Significance
of Lipopolysaccharide from Legionella Pp.
96-107
Marta Palusinska-Szysz and Ryszard Russa
[Abstract] [Purchase
Issue/Articles]
A New Approach to the Inflammatory/Autoimmune
Diseases Pp. 108-113
Maria E. Ferrero
[Abstract] [Purchase
Issue/Articles]
Social Leverage of Intellectual Property:
Road to the Development of Better Therapy for Tuberculosis
Pp. 114-122
Harry Thangaraj and Rajko Reljic
[Abstract] [Purchase
Issue/Articles]
Epidemiology, Pathogenicity and Emerging
Resistances in Staphylococcus pasteuri:
From Mammals and Lampreys, to Man Pp. 123-129
Vincenzo Savini, Chiara Catavitello, Azaira Bianco,
Andrea Balbinot and Domenico D’Antonio
[Abstract] [Purchase
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Topical Applications of Ozone and Ozonated
Oils as Anti-Infective Agents: An Insight into the Patent
Claims Pp. 130-142
Valter Travagli, Iacopo Zanardi and
Velio Bocci
[Abstract] [Purchase
Issue/Articles]
Descending Necrotizing Mediastinitis of Odontogenic
Origin Pp. 143-150
Matteo Biasotto, Silvia Chiandussi, Fulvia Costantinides
and Roberto Di Lenarda
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Patent Selections Pp. 151-153
Abstracts
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Novel Antibiotic Compounds Produced by the
Insect Pathogenic Bacterium Photorhabdus
Ioannis G. Eleftherianos
Phototorhabdus is an insect pathogenic enterobacterium
which maintains a mutualistic interaction with heterorhabditid
nematodes. While the bacteria live in the nematode gut, the
nematodes live in the soil and infect insect larvae, releasing
their symbiotic bacteria into the insect blood. Here the bacteria
reproduce and kill the insect by septicaemia. The nematodes
then feed on the bacterial biomass and undergo several rounds
of reproduction before emerging from the cadaver carrying
their bacterial symbionts. Photorhabdus secretes
a versatile armory of antimicrobial molecules into the insect
corpse. These biocides exert a range of antimicrobial killing
activities and serve a dual function. They minimize competition
from non-symbiotic bacteria and prevent microbial putrefaction
of the nematode-infected insect cadaver. The goal of this
review is to describe current knowledge of the molecular mechanisms
involved in the production of bacteriocins by Photorhabdus.
Recent important advances in identifying novel potent antibiotic
compounds from Photorhabdus and elucidating their
complex mode of action in relation to pathogenicity and symbiosis
associations are also discussed. The last part of this review
focuses on the potential role Photorhabdus antibiotics
may play in contributing to the discovery of novel pharmaceutical
and agrochemical products. The present article is a short
review of recent patents on Photohabdus.
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Hybolites: Novel Therapeutic Tools for Targeting Hyperstructures
in Bacteria
Guillaume Legent and Victor
Norris
The scarcity of new molecules that can act on bacteria
is a major problem. New strategies for developing such molecules
might be based on recent concepts in microbiology. Hyperstructures
are large assemblies of molecules and macromolecules that
perform functions such as DNA replication, RNA degradation
and chemotaxis and the interactions between hyperstructures
have been proposed to constitute an intermediate level of
organisation in cells. Functioning-dependent hyperstructures
form in the presence of their substrate and dissociate in
its absence. An entirely new therapy for bacterial diseases
might therefore be devised based on the manipulation of hyperstructures.
One way to do this would be to supply cells with hybrid metabolites
or hybolites made by a pairwise, covalently linked
combination of the thousands of small molecules involved in
metabolism. Some of these hybolites would be substrates for
two, very different, hyperstructures and might do much more
than simply inhibit key enzymes and processes within the hyperstructures:
they might provoke the assembly of two hyperstructures in
the same space or lead to hyperstructures emitting misleading
signals. It is conceivable that hybolites might even convert
a pathogenic Mr Hyde into an inoffensive Dr Jekyll. The article
also discusses the major patent applications of hyperstructures
in bacteria.
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Chemical Structure and Biological Significance of Lipopolysaccharide
from Legionella
Marta Palusinska-Szysz and
Ryszard Russa
Legionella are aerobic, gram-negative, motile, rod-shaped
bacteria, which form a distinct taxonomic unit within the
γ -
2 subdivision of the Proteobacteria. The reservoirs
of Legionella are natural or man-made water systems
where the bacteria survive and disseminate as obligate intracellular
parasites of free living protozoa. In the human lung, the
bacteria invade alveolar macrophages inducing the potentially
lethal pneumonia commonly known as Legionnaires’ disease.
Although all Legionella species are considered potentially
pathogenic for humans, Legionella pneumophila is
the aetiological agent responsible for most reported cases
of community- and nosocomially-acquired legionellosis. The
O-polysaccharide in the lipopolysaccharide of L. pneumophila
is composed of a repeating homopolymer of α
-(2→4)-linked
5,7-diamino-3,5,7,9-tetradeoxy-D-glycero-D-galacto-non-2-ulosonic
acid (legionaminic acid). The outer region of the core enriched
with 6-deoxy sugars and N- and O- acetylated
sugars as well as the highly N- and O-acylated
O-chain contribute to a high hydrophobicity of the bacterial
surface, which enables these bacteria to spread. Lipids A
from Legionella contain a backbone with 2,3-diamino-2,3-dideoxy-D-glucose
and unusual fatty acids. The present article indicates some
patents useful in the diagnostics of Legionnaires’ disease.
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A New Approach to the Inflammatory/Autoimmune Diseases
Maria E. Ferrero
Extracellular adenosine 5´-triphosphate (eATP)
is an important mediator of cell-to-cell interactions in the
nervous, vascular and immune system. Its low release by different
cells, as mast cells, platelets, red blood cells, T cells
and also by nerve terminals, requires different mechanisms
and especially occurs in physiologic conditions. However,
in pathologic conditions, as inflammation, eATP can highly
increase, following its release by damaged cells. Elevated
levels of eATP provoke the activation of some purinergic receptors,
mainly the P2XR, which are located on mononuclear phagocytes,
T cells and endothelial cells. The activation by eATP of inflammatory/immune
cells leads to their release of some inflammatory mediators,
such as the cytokines IL-1β
and TNFα.
These cytokines are able to further activate other cells,
as endothelial cells, favouring their increased expression
of adhesion molecules; such process enhances circulating cell
recruitment to the inflamed tissue. The blockade of the purinergic-mediated
activation of the inflammatory/immune cells might represent
a useful tool to reduce the spreading of the inflammatory/immune
response. This review will summarize the beneficial effects
of the use of periodate oxidized ATP (oATP), an inhibitor
of P2XR, in the treatment of some experimental models of inflammatory/immune
diseases. The article is a short review of recent patents
related to the anti-inflammatory/analgesic/antiangiogenic
effects of oATP and to its role in the autoimmune diseases.
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Social Leverage of Intellectual Property: Road to the Development
of Better Therapy for Tuberculosis
Harry Thangaraj and Rajko Reljic
Current TB drug development is beset with many problems.
There is a perceived lack of commercial return on investment,
as the vast majority of TB patients come from impoverished
areas of the world. Clinical trials for new TB drugs are complex,
protracted and very expensive. Therefore, the development
of new anti-tuberculosis drugs requires simultaneous forward
planning of the design of the trials that will be required
for licensing purposes. In this article we briefly review
the current state of new TB drug development and discuss issues
related to intellectual property (IP), with a special emphasis
on how IP can facilitate rather than hinder the development
of better TB drugs. We also list and discuss the major patent
applications that underpin TB drugs that have entered prominent
clinical trials and additional applications that were filed
over the last five years for drugs resulting from basic upstream
research.
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Epidemiology, Pathogenicity and Emerging Resistances in Staphylococcus
pasteuri: From Mammals and Lampreys, to Man
Vincenzo Savini, Chiara Catavitello, Azaira Bianco,
Andrea Balbinot and Domenico D’Antonio
Staphylococcus pasteuri is a coagulase-negative, Gram
positive organism which is emerging as an agent of nosocomial
infections and a blood derivatives contaminant, though its
role in causing human disease mostly remains controversial.
Despite the paucity of isolates recovered, this bacterium
has recently appeared to express resistance against several
classes of antibiotic compounds, such as methicillin/oxacillin,
macrolides, lincosamides, streptogramins, tetracyclines, chloramphenicol,
streptomycin, fosfomycin, as well as quaternary ammonium compounds.
Also, authors will discuss some essential patents related
to the topic reviewed.
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Topical Applications of Ozone and Ozonated Oils as Anti-Infective
Agents: An Insight into the Patent Claims
Valter Travagli, Iacopo Zanardi and
Velio Bocci
Orthodox medicine has been very active in the field of
topical anti-infective agents and current chemotherapy has
procured valid antibiotics, antivirals, vaccines, antibodies,
and antiparasitic drugs to be parenterally and/or topically
used. However, these drugs may cause side effects and sometimes
provide unsatisfactory results because pathogens become drug-resistant.
Another drawback is represented by their cost, which compromise
their use or their availability in poor Countries. Therefore,
there is a critical need for new strategies to treat dermatological
affections. The old intuition for using ozone in the treatment
of necrotic wounds, especially if due to anaerobic bacteria,
is now justified by the studies about reactive oxygen species
generation by granulocytes and macrophages as the first line
of defense during an infection. As a consequence, the disinfectant
value of ozone has been increasingly appreciated during the
last fifteen years. This review summarizes the patents filed
and issued, with particular emphasis to the more recent patents,
about the anti-infective topical use of ozone: i) in the gaseous
form; ii) after gaseous ozone saturation of aqueous, not-oily
pharmaceutical vehicles and solvents; iii) where gaseous ozone
chemically reacts with unsaturated substrates leading to therapeutically
active ozonated derivatives. We hope that recent advances
and a better understanding of the ozone chemistry and biology
will be able to create the mental attitude to prove the validity
of large-scale therapeutic use of both ozone and ozone derivatives
as topical anti-infective agents by performing multicenter,
randomized clinical studies, as aptly requested by orthodox
medicine.
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Descending Necrotizing Mediastinitis of Odontogenic
Origin
Matteo Biasotto, Silvia Chiandussi, Fulvia Costantinides
and Roberto Di Lenarda
Descending Necrotizing Mediastinitis is a rare complication
that can be secondary to dental infections or surgical procedures
involving the oral region. Despite a prompt pharmacological
therapy and surgical intervention, a delayed diagnosis is
still responsible for a too high mortality rate (about 40%).
We present a review of the current literature on Descending
Necrotizing Mediastinitis, focusing on the evolution of its
management from Pearse to today. In particular, recent patents
focused on novel compositions and methods to prevent and treat
oral infections.
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