CAMBRIDGE, Mass. -- (BUSINESS WIRE) --
Spero Therapeutics, LLC, a biopharmaceutical company founded to develop
novel therapies for treatment of bacterial infections, today announced
that data on the original compounds that serve as the foundational
research for the company’s MvfR inhibitor program will be presented at
the 54th Interscience Conference on Antimicrobial Agents and
Chemotherapy (ICAAC). Spero will present data in symposium and poster
sessions showing activity of MvfR inhibitors against Pseudomonas
aeruginosa bacteria. The conference will take place on September
5-9th at the Walter E. Washington Convention Center, Washington, DC.
Session # 144
Title: Alternative Treatment Approaches for Bacterial Infections.
Speaker: Laurence G. Rahme, Massachusetts General Hospital/Harvard
Medical School, Boston, Mass.
Session Type: Symposium
Topic: Inhibition of Pseudomonas aeruginosa MvfR Reduces Acute
Virulence and Chronic Infection Phenotypes
Date: Monday, September 8, 2014
Presentation Time: 8:30 to 10:30 AM
Location: Room 143 A
Infections caused by Gram-negative bacterial pathogens are becoming
increasingly difficult to treat due to resistance to current
antibacterial drugs. There is an urgent need to identify new
antimicrobial drugs that will help circumvent the current antibiotic
Bacterial pathogens often develop resistance to antibiotic drugs that
target bacterial growth or viability. However strategies that
specifically target virulence pathways non-essential for growth could
limit selection for resistance.
This study examines the bacterial communication system MvfR (PqsR),
which is known to control virulence of the opportunistic bacterial
pathogen P. aeruginosa. Small molecule compounds were
identified and optimized that effectively silenced the MvfR
communication system, and as a result blocked P. aeruginosa
virulence both in vitro and in vivo.
These new compounds are the first known to restrict the ability of
bacteria to form antibiotic-tolerant cells and consequently proved to
be very effective at preventing persistent infection in a mammalian
Conclusion: Because of their ability to simultaneously block acute and
persistent infections, these new molecules may provide a strong basis
for the development of next generation antimicrobials.
Session # 168
Title: Advances against Gram-Negative Pathogens
Poster Title: Identification of Anti-Virulence Compounds that Disrupt
Regulated Acute and Persistent Pathogenicity
Presentation # F-1555
Authors: M. Starkey #1, F. Lepine #2, D. Maura #1,
A. Bandyopadhaya1, B. Lesic1, J. He1,
T. Kitao1, V. Righi1, S. Milot2, A. A.
Tzika1, L. G. Rahme1;
1Massachusetts Gen. Hosp., Harvard Med. Sch., Shriners Hosp.,
Boston, MA, 2INRS-Inst. Armand Frappier, Laval, QC, Canada
Date: Monday, Sep 08, 2014
Presentation Time: 11:00 AM - 1:00 PM
Location: Exhibit Hall B
Etiological agents of acute, persistent, or relapsing clinical
infections - such as Pseudomonas aeruginosa - are often
refractory to antibiotics due to multidrug resistance and/or
Forty MvfR-regulon inhibitors, that specifically inhibit infection
without affecting bacterial growth or viability to mitigate resistance
selection, were identified using a whole-cell, high-throughput screen
of ~300,000 compounds. Subsequently the potency of the compounds was
As a result, these inhibitors reduced P. aeruginosa virulence in
vivo in both murine acute lung infection or burn infection models.
In addition, these compounds reduced antibiotic-tolerant persisters
formation by inhibiting the pro-persistent QS molecule 2-AA, and
consequently proved to be very effective at preventing persistent
infection in mice.
Conclusion: Molecules targeting the MvfR-regulated P. aeruginosa
quorum sensing (QS) virulence pathway provide for the development of
next-generation clinical therapeutics to treat deleterious
bacterial-human infections refractory to existing therapies.
Spero is a product-focused biopharmaceutical company developing a
pipeline of novel treatments for bacterial infections and is located in
Cambridge, Massachusetts. Spero’s MvfR inhibitor program works
differently from existing antibiotics by targeting a pathway involved in
two critical bacterial processes: virulence and persistence. Spero’s
drug candidates may uniquely reduce the morbidity caused by severe
infections and promote their clearance, including in bacterial strains
highly resistant to even the most potent existing antibiotics. For more
information, please visit www.sperotherapeutics.com.
Copyright © Business Wire 2014
Ankit Mahadevia, M.D., 617-588-2600
Partner at Atlas Ventures
Maureen L. Suda, 585-387-9248