Recent Patents on Biotechnology (v.10, #2)

Meet Our Associate Editor by Ipsita Roy (143-143).

Background: Pigment production is regulated by quorum-sensing (QS) in certain bacteria which are being widely used as model organisms in different QS labs. This paper emphasizes importance of selecting an appropriate wavelength for quantification of bacterial growth and pigmentation. While screening different natural/synthetic preparations for their possible QSmodulating potential, it becomes very much necessary to establish that the observed effect is truly QS-associated, and not falsely inflated owing to inaccurate quantification of bacterial cell density/ pigment intensity.
Methods: Pigments were extracted in suitable organic solvents, whereas quantification of bacterial growth and extracted pigments was done photometrically.
Results: Findings reported in this paper, suggest that while quantifying cell density in a pigmented bacterial suspension, such a wavelength (e.g. 764 nm) should be selected at which pigment interference is either absent or minimum. Additionally, importance of appropriate dilution of the bacterial cell suspensions, prior to photometric measurement has been highlighted.
Conclusion: This work indicates that while working with pigmented bacteria, it is important to pay attention to the absorption spectrum of the pigment(s) involved, and also to dilute the dense bacterial suspensions appropriately prior to measuring optical density, so as to avoid any major deviation of OD from the proportionality to the cell density. Besides presenting the experimental data in this paper, patents regarding measurement of cell growth, as well as those indicating the potential of commercialization of various aspects of QS research have been mentioned.

Phytochemicals as Effective Quorum Quenchers Against Bacterial Communication by Sivaramakrishnan Subramaniyan, Sasikumar Divyasree, Girija Sadasivan Sandhia (153-166).
Background: Quorum sensing or the bacterial information flow in an orchestrated manner is an essential feature of many pathogenic bacteria. Quorum quenching molecules (QQ) can inhibit the growth of such bacteria.
Objective: The purpose of this study is to evaluate the potential of plant extracts as quorum quenchers and monitor the recent patents.
Methods: Many available reports and patents are on synthetic ligand molecules or even compounds isolated from cyanobacteria (Honaucin A) and other microorganisms inhibiting quorum sensing molecules. Molecules with Quorum quenching (QQ) ability isolated from plants could inhibit violacein and pyocyanin production in Chromobacterium violaceum and Pseudomonas aeruginosa respectively.
Results: Studies leading to patents are initiated in this comparatively new topic. Hydrolysable tannins such as vescalagin and castalagin isolated from Conocarpus erectus are reported to have anti- quorum sensing activity. The gene product of agr D in gram positive bacteria is modified by endopeptidase to thiolactone peptide which is equivalent to acyl homoserine lactone of gram negative bacteria. General pathways suggested for the quorum sensing inhibition by plant extracts focuses on such autoinducers.
Conclusion: Medicinal plants and plant extracts are the leading sources of quorum sensing inhibitors. Patents related to quorum sensing inhibitors are taking new leaps in medicine, especially applications relating to the addition of quorum sensing inhibitors on to the surface of implantable or indwelling devices that are helpful in eradicating the trouble of infection in health care industry.

Natural Compounds for Overcoming Multidrug Resistance in Mycobacteria by Sharda Sharma, Saif Hameed, Zeeshan Fatima (167-174).
Background: Tuberculosis caused by Mycobacterium tuberculosis (MTB) is currently a major health concern due to its growing mortality rates around the world. The known anti-TB drugs although are available for the treatment but it produces adverse side effects on the human health and are also not very cost effective. Moreover, emergence of multidrug resistance (MDR) phenomenon has also compromised their activities.
Objective: Hence there is an urgent need to search novel drugs and compounds from natural sources having lesser side effects which have proved to be vital and widely used nowadays. Many recent studies have been established which show promising antimycobacterial activities against MTB.
Result: This review summarizes the various naturally occurring active compounds acting on different targets against MTB. Moreover, it also deals with the compounds having patent perspective.
Conclusion: Together, the article laid emphasis on reverting towards the natural compounds so that further work is carried out to exploit their therapeutic interventions.

Recent Advancements in Antimycobacterial and Antifungal Drugs: A Patent Perspective by Zeeshan Fatima, Rahul Pal, Moiz Ashraf Ansari, Saif Hameed (175-183).
Background: Infections caused by Mycobacterium and pathogenic fungi have risen drastically over the past few decades. Moreover, with the increase in the number of immunocompromised (burn, organ transplant, chemotherapy, HIV) patients, these bacterial and fungal infections have led to alarming mortality rates. The drugs currently in use have become relatively ineffective due to ever increasing phenomenon of multidrug resistance. Furthermore, these drugs suffer with severe toxicity effects and also lack cost effectiveness.
Objective: Under such compelling circumstances, it is pertinent to find novel and safer drugs with improved properties. One strategy that could be adopted is to identify natural bioactive compounds having antimicrobial potential with minimal side effects. Alternatively, drugs synthesized with the help of combinatorial chemistry leading to enhanced antimicrobial properties could be another strategy.
Result: This article summarizes at a common platform the current scenario of the available natural as well as synthetic drugs targeting cell envelope that have patentable therapeutic interventions against predominant human bacterial and fungal pathogens.

Bacteriophage for Mitigation of Multiple Drug Resistant Biofilm Forming Pathogens by Shilpa Deshpande Kaistha, Pramila Devi Umrao (184-194).
Background: Microbial communities encased in exopolymeric substances (EPS) attached to suitable substrate as biofilms show heightened resistance to multiple drugs including antibiotics. One promising control strategy in dealing with the ever mounting problem of antibiotic resistance amongst biofilm forming bacterial pathogens is the use of biological agents.
Objective: This review focuses on the development of bacteriophages as means of disrupting biofilm forming pathogens and hence mitigation of multiple drug resistant organisms.
Results: Bacteriophages are obligatory viral intracellular parasites that can cause lytic infection of their bacterial hosts. Bacteriophage (Phage) therapy is advantageous in being highly host specific, safe and non-toxic to humans and hence environmental friendly. Bacteriophage induced lysis of cells within the biofilm is aided by the production of penetrating enzymes such as endolysins and EPS depolymerases as well quorum sensing inhibitors such as lactonases.
Conclusion: Phages are a promising alternative therapy for the control of multiple drug resistant (MDR) pathogens. Several phage (indigenous and engineered)/ phage products are currently being patented and developed as commercial biological control agents.

Background: Antibiotic resistance is a growing threat in the treatment of bacterial diseases. Bacterial invasion and its virulence can cause damage to the host cells via quorum sensing mechanism which is responsible for the intercellular communication among bacteria that regulates expression of many genes. Quorum sensing (QS) differentially expresses specific sets of genes which may produce resistance. Researchers have been devoted to develop more potent compounds against bacterial resistant quorum sensing inhibitors.
Methods: A number of anti-quorum sensing approaches have been documented to screen potent inhibitors against quorum sensing induced bacterial virulence. Experimental screening of a large chemical compound library against a quorum sensing biological target is an established technology for lead identification but it is expensive, laborious and time consuming. Therefore, computer-aided high throughput ligand and structure based virtual screening are most effective pharmacoinformatic tools prior to experiment in this context.
Results: Ligand based screening includes quantitative structure-activity relationship (QSAR) and pharmacophore generation whereas techniques of structure based virtual screening include molecular docking. The study in this direction can increase the findings of hit rates and decrease cost of drug design and development by producing potent natural as well as synthetic anti-quorum sensing compounds.
Conclusion: Most recent patent coverage on ligand and structure based design of novel bioactive quorum sensing inhibitors has been presented here. The paper has also critically reviewed the screening and design of potent quorum sensing inhibitor leads that would help in patenting novel leads active against bacterial virulence and minimizing antibiotic resistance among bacterial pathogens.

Caenorhabditis elegans: A Model for Studying Human Pathogen Biology by Nabila Sorathia, Medha S. Rajadhyaksha (217-225).
Novel clinical strategies need to be evolved, as pathogens, especially the ones that infect the human, develop resistance. To do so, host pathogen biology needs to be clearly understood and this can be done using a nematode worm, Caenorhabditis elegans, which harbours the same virulent microbes. Over several decades, the worm has been used to study host-microbe interaction with reference to immune response of the worm, antimicrobial molecules secreted, cell death in the worm body, quorum sensing network of the bacteria and fast or slow worm death. This mini review gives a bird's eye view of the directions that have been taken in these areas to date. Currently, the worm has been proposed to be an ideal model for high throughput screening of natural and synthetic drugs against a variety of bacteria. Experimental systems that allow this screening have been patented. Caenorhabditis elegans, thus, is one of the very effective models for studying pathogens that infect human.

Patent Selection (226-226).