Technology 2018-03-29T03:37:00+00:00

Technology

Accelerate your antibiotic discovery research with Bacterial Cytological Profiling (BCP).  BCP uses quantitative cell biology methods to study how different conditions or drugs affect the overall cytological characteristics of microbial cells.  BCP detects disturbances in all essential cellular pathways in a single, rapid test, making it a powerful antibiotic discovery platform.

Activity
BCP directly identifies the mode of action (MOA) of new candidates, information key to identifying molecules hitting new targets and for advancing these hits through the drug development pipeline. BCP reports MOA information for 100% of the hits obtained from screening, allowing investigators to immediately focus on the best hits in their collection.

Sensitivity
BCP can detect cytological changes that do not kill or even impair growth, making it highly sensitive and allowing the discovery of molecules previously missed by other whole cell-based screens. The technology can also identify compounds that alter the cell in critical ways useful for developing new treatments. For example, BCP can identify compounds that permeabilize the outer membrane of Gram negative bacteria without affecting the inner membrane or cell growth. Such permeabilization agents sensitize bacteria to many clinically approved compounds and can be used in combination therapy to enhance susceptibility of Gram negative pathogens to many conventional antibiotics.

Versatility
BCP works with all types of potential antimicrobial compounds, including small synthetic chemicals, crude natural product extracts, fractionated natural products, peptides, or synthetic molecules that mimic peptides. BCP can identify molecules that have multiple MOAs which are traditionally more difficult to characterize but highly desired due to their inherently low rates of resistance. Similarly, BCP can distinguish different MOAs which may arise in a mixture of molecules or a natural product extract.

Scalability
Linnaeus has also developed a high throughput version of BCP (HTP-BCP) for identifying hits from large chemical or natural product libraries with unparalleled sensitivity.

Publications

Arylthiazole antibiotics targeting intracellular methicillin-resistant Staphylococcus aureus (MRSA) that interfere with bacterial cell wall synthesis
Eid I., Elsebaei M.M., Mohammad H., Hagras M., Peters C.E., Hegazy Y.A., Cooper B., Pogliano J., Pogliano K., Abulkhair H.S., Seleem M.N., Mayhoub A.S.
2017 European Journal of Medicinal Chemistry

Phenylthiazole Antibacterial Agents Targeting Cell Wall Synthesis Exhibit Potent Activity in Vitro and in Vivo against Vancomycin-Resistant Enterococci
Mohammad, H., Younis, W., Chen, L., Peters, C.E., Pogliano, J., Pogliano, K., Cooper, B., Zhang, J., Mayhoub, A., Oldfield, E.,  Cushman, M., Seleem, M.N.
2017 Journal of Medicinal Chemistry

Bacteriological profiling of diphenylureas as a novel class of antibiotics against methicillin-resistant Staphylococcus aureus
Mohammad, H., Younis, W., Ezzat, H.G., Peters, C.E., AbdelKhalek, A., Cooper, B., Pogliano, K., Pogliano, J., Mayhoub, A.S., Seleem, M.N.
2017 PLOS ONE

Rapid Inhibition Profiling in Bacillus subtilis to Identify the Mechanism of Action of New Antimicrobials
Lamsa, A., Lopez-Garrido, J., Quach, D., Riley, E. P., Pogliano, J., and Pogliano, K.
2016 ACS Chemical Biology

Bacterial Cytological Profiling (BCP) as a Rapid and Accurate Antimicrobial Susceptibility Testing Method for Staphylococcus aureus
Quach D.T., Sakoulas G., Nizet V., Pogliano J., Pogliano K.
2016 EBioMedicine

Application of bacterial cytological profiling to crude natural product extracts reveals the antibacterial arsenal of Bacillus subtilis
Nonejuie, P., Trial, R. M., Newton, G. L., Lamsa, A., Ranmali Perera, V., Aguilar, J., Liu, W. T., Dorrestein, P. C., Pogliano, J., and Pogliano, K.
2016 Journal of Antibiotics

Azithromycin Synergizes with Cationic Antimicrobial Peptides to Exert Bactericidal and Therapeutic Activity Against Highly Multidrug-Resistant Gram-Negative Bacterial Pathogens
Lin L., Nonejuie P., Munguia J., Hollands A., Olson J., Dam Q., Kumaraswamy M., Rivera H. Jr, Corriden R., Rohde M., Hensler M.E., Burkart M.D., Pogliano J., Sakoulas G., Nizet V.
2015 EBioMedicine

Small-Molecule Inhibitors of Gram-Negative Lipoprotein Trafficking Discovered by Phenotypic Screening
McLeod, S.M., Fleming, P.R., MacCormack, K., McLaughlin, R.E., Whiteaker, J.D., Narita, S., Mori, M., Tokuda, H., Miller, A.A.
2015 Journal of Bacteriology

Bacterial cytological profiling rapidly identifies the cellular pathways targeted by antibacterial molecules
Nonejuie P., Burkart M., Pogliano K., Pogliano J.
2013  Proceedings of the National Academy of Sciences (PNAS)

The Bacillus subtilis cannibalism toxin SDP collapses the proton motive force and induces autolysis
Lamsa, A., Lui, W.T., Dorrestein, P.C. , Pogliano, K.
2012 Molecular Microbiology