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Targeting Multidrug-Resistant Acinetobacter spp.: Sulbactam and the Diazabicyclooctenone β-Lactamase Inhibitor ETX2514 as a Novel Therapeutic Agent.

Barnes MD, Kumar V, Bethel CR, Moussa SH, O'Donnell J, Rutter JD, Good CE, Hujer KM, Hujer AM, Marshall SH, Kreiswirth BN, Richter SS, Rather PN, Jacobs MR, Papp-Wallace KM, van den Akker F, Bonomo RA.

MBio. 2019 Mar 12;10(2). pii: e00159-19. doi: 10.1128/mBio.00159-19.


Beyond piperacillin-tazobactam: cefepime and AAI101 as a potent β-lactam-β-lactamase inhibitor combination.

Papp-Wallace KM, Bethel CR, Caillon J, Barnes MD, Potel G, Bajaksouzian S, Rutter JD, Reghal A, Shapiro S, Taracila MA, Jacobs MR, Bonomo RA, Jacqueline C.

Antimicrob Agents Chemother. 2019 Mar 11. pii: AAC.00105-19. doi: 10.1128/AAC.00105-19. [Epub ahead of print]


Whole Genome Sequence Analysis of Burkholderia contaminans FFH2055 Strain Reveals the Presence of Putative β-Lactamases.

Degrossi JJ, Merino C, Isasmendi AM, Ibarra LM, Collins C, Bo NE, Papalia M, Fernandez JS, Hernandez CM, Papp-Wallace KM, Bonomo RA, Vazquez MS, Power P, Ramirez MS.

Curr Microbiol. 2019 Apr;76(4):485-494. doi: 10.1007/s00284-019-01653-4. Epub 2019 Feb 19.


"Resurrecting old β-lactams": the potent inhibitory activity of temocillin against multi-drug resistant Burkholderia spp. isolates from the United States.

Zeiser ET, Becka SA, Barnes MD, Taracila MA, LiPuma JJ, Papp-Wallace KM.

Antimicrob Agents Chemother. 2019 Feb 4. pii: AAC.02315-18. doi: 10.1128/AAC.02315-18. [Epub ahead of print]


Deciphering the Evolution of Cephalosporin Resistance to Ceftolozane-Tazobactam in Pseudomonas aeruginosa.

Barnes MD, Taracila MA, Rutter JD, Bethel CR, Galdadas I, Hujer AM, Caselli E, Prati F, Dekker JP, Papp-Wallace KM, Haider S, Bonomo RA.

MBio. 2018 Dec 11;9(6). pii: e02085-18. doi: 10.1128/mBio.02085-18.


Characterization of the AmpC β-Lactamase from Burkholderia multivorans.

Becka SA, Zeiser ET, Barnes MD, Taracila MA, Nguyen K, Singh I, Sutton GG, LiPuma JJ, Fouts DE, Papp-Wallace KM.

Antimicrob Agents Chemother. 2018 Sep 24;62(10). pii: e01140-18. doi: 10.1128/AAC.01140-18. Print 2018 Oct.


Sequence heterogeneity of the PenA carbapenemase in clinical isolates of Burkholderia multivorans.

Becka SA, Zeiser ET, Marshall SH, Gatta JA, Nguyen K, Singh I, Greco C, Sutton GG, Fouts DE, LiPuma JJ, Papp-Wallace KM.

Diagn Microbiol Infect Dis. 2018 Nov;92(3):253-258. doi: 10.1016/j.diagmicrobio.2018.06.005. Epub 2018 Jun 18.


Strategic Approaches to Overcome Resistance against Gram-Negative Pathogens Using β-Lactamase Inhibitors and β-Lactam Enhancers: Activity of Three Novel Diazabicyclooctanes WCK 5153, Zidebactam (WCK 5107), and WCK 4234.

Papp-Wallace KM, Nguyen NQ, Jacobs MR, Bethel CR, Barnes MD, Kumar V, Bajaksouzian S, Rudin SD, Rather PN, Bhavsar S, Ravikumar T, Deshpande PK, Patil V, Yeole R, Bhagwat SS, Patel MV, van den Akker F, Bonomo RA.

J Med Chem. 2018 May 10;61(9):4067-4086. doi: 10.1021/acs.jmedchem.8b00091. Epub 2018 Apr 20.


Relebactam Is a Potent Inhibitor of the KPC-2 β-Lactamase and Restores Imipenem Susceptibility in KPC-Producing Enterobacteriaceae.

Papp-Wallace KM, Barnes MD, Alsop J, Taracila MA, Bethel CR, Becka SA, van Duin D, Kreiswirth BN, Kaye KS, Bonomo RA.

Antimicrob Agents Chemother. 2018 May 25;62(6). pii: e00174-18. doi: 10.1128/AAC.00174-18. Print 2018 Jun.


Inactivation of the Pseudomonas-Derived Cephalosporinase-3 (PDC-3) by Relebactam.

Barnes MD, Bethel CR, Alsop J, Becka SA, Rutter JD, Papp-Wallace KM, Bonomo RA.

Antimicrob Agents Chemother. 2018 Apr 26;62(5). pii: e02406-17. doi: 10.1128/AAC.02406-17. Print 2018 May.


Probing the Mechanism of Inactivation of the FOX-4 Cephamycinase by Avibactam.

Nukaga M, Papp-Wallace KM, Hoshino T, Lefurgy ST, Bethel CR, Barnes MD, Zeiser ET, Johnson JK, Bonomo RA.

Antimicrob Agents Chemother. 2018 Apr 26;62(5). pii: e02371-17. doi: 10.1128/AAC.02371-17. Print 2018 May.


Klebsiella pneumoniae Carbapenemase-2 (KPC-2), Substitutions at Ambler Position Asp179, and Resistance to Ceftazidime-Avibactam: Unique Antibiotic-Resistant Phenotypes Emerge from β-Lactamase Protein Engineering.

Barnes MD, Winkler ML, Taracila MA, Page MG, Desarbre E, Kreiswirth BN, Shields RK, Nguyen MH, Clancy C, Spellberg B, Papp-Wallace KM, Bonomo RA.

MBio. 2017 Oct 31;8(5). pii: e00528-17. doi: 10.1128/mBio.00528-17.


A 17-Year Nationwide Study of Burkholderia cepacia Complex Bloodstream Infections Among Patients in the United States Veterans Health Administration.

El Chakhtoura NG, Saade E, Wilson BM, Perez F, Papp-Wallace KM, Bonomo RA.

Clin Infect Dis. 2017 Oct 15;65(8):1253-1259. doi: 10.1093/cid/cix559.


Potent β-Lactam Enhancer Activity of Zidebactam and WCK 5153 against Acinetobacter baumannii, Including Carbapenemase-Producing Clinical Isolates.

Moya B, Barcelo IM, Bhagwat S, Patel M, Bou G, Papp-Wallace KM, Bonomo RA, Oliver A.

Antimicrob Agents Chemother. 2017 Oct 24;61(11). pii: e01238-17. doi: 10.1128/AAC.01238-17. Print 2017 Nov.


Avibactam Restores the Susceptibility of Clinical Isolates of Stenotrophomonas maltophilia to Aztreonam.

Mojica MF, Papp-Wallace KM, Taracila MA, Barnes MD, Rutter JD, Jacobs MR, LiPuma JJ, Walsh TJ, Vila AJ, Bonomo RA.

Antimicrob Agents Chemother. 2017 Sep 22;61(10). pii: e00777-17. doi: 10.1128/AAC.00777-17. Print 2017 Oct.


Exploring the Landscape of Diazabicyclooctane (DBO) Inhibition: Avibactam Inactivation of PER-2 β-Lactamase.

Ruggiero M, Papp-Wallace KM, Taracila MA, Mojica MF, Bethel CR, Rudin SD, Zeiser ET, Gutkind G, Bonomo RA, Power P.

Antimicrob Agents Chemother. 2017 May 24;61(6). pii: e02476-16. doi: 10.1128/AAC.02476-16. Print 2017 Jun.


WCK 5107 (Zidebactam) and WCK 5153 Are Novel Inhibitors of PBP2 Showing Potent "β-Lactam Enhancer" Activity against Pseudomonas aeruginosa, Including Multidrug-Resistant Metallo-β-Lactamase-Producing High-Risk Clones.

Moya B, Barcelo IM, Bhagwat S, Patel M, Bou G, Papp-Wallace KM, Bonomo RA, Oliver A.

Antimicrob Agents Chemother. 2017 May 24;61(6). pii: e02529-16. doi: 10.1128/AAC.02529-16. Print 2017 Jun.


Overcoming an Extremely Drug Resistant (XDR) Pathogen: Avibactam Restores Susceptibility to Ceftazidime for Burkholderia cepacia Complex Isolates from Cystic Fibrosis Patients.

Papp-Wallace KM, Becka SA, Zeiser ET, Ohuchi N, Mojica MF, Gatta JA, Falleni M, Tosi D, Borghi E, Winkler ML, Wilson BM, LiPuma JJ, Nukaga M, Bonomo RA.

ACS Infect Dis. 2017 Jul 14;3(7):502-511. doi: 10.1021/acsinfecdis.7b00020. Epub 2017 Mar 30.


Can Ceftazidime-Avibactam and Aztreonam Overcome β-Lactam Resistance Conferred by Metallo-β-Lactamases in Enterobacteriaceae?

Marshall S, Hujer AM, Rojas LJ, Papp-Wallace KM, Humphries RM, Spellberg B, Hujer KM, Marshall EK, Rudin SD, Perez F, Wilson BM, Wasserman RB, Chikowski L, Paterson DL, Vila AJ, van Duin D, Kreiswirth BN, Chambers HF, Fowler VG Jr, Jacobs MR, Pulse ME, Weiss WJ, Bonomo RA.

Antimicrob Agents Chemother. 2017 Mar 24;61(4). pii: e02243-16. doi: 10.1128/AAC.02243-16. Print 2017 Apr.


Exploring the Role of the Ω-Loop in the Evolution of Ceftazidime Resistance in the PenA β-Lactamase from Burkholderia multivorans, an Important Cystic Fibrosis Pathogen.

Papp-Wallace KM, Becka SA, Taracila MA, Zeiser ET, Gatta JA, LiPuma JJ, Bonomo RA.

Antimicrob Agents Chemother. 2017 Jan 24;61(2). pii: e01941-16. doi: 10.1128/AAC.01941-16. Print 2017 Feb.


New β-Lactamase Inhibitors in the Clinic.

Papp-Wallace KM, Bonomo RA.

Infect Dis Clin North Am. 2016 Jun;30(2):441-464. doi: 10.1016/j.idc.2016.02.007. Review.


Treatment options for infections caused by carbapenem-resistant Enterobacteriaceae: can we apply "precision medicine" to antimicrobial chemotherapy?

Perez F, El Chakhtoura NG, Papp-Wallace KM, Wilson BM, Bonomo RA.

Expert Opin Pharmacother. 2016;17(6):761-81. doi: 10.1517/14656566.2016.1145658. Epub 2016 Mar 9. Review.


Boronic Acid Transition State Inhibitors Active against KPC and Other Class A β-Lactamases: Structure-Activity Relationships as a Guide to Inhibitor Design.

Rojas LJ, Taracila MA, Papp-Wallace KM, Bethel CR, Caselli E, Romagnoli C, Winkler ML, Spellberg B, Prati F, Bonomo RA.

Antimicrob Agents Chemother. 2016 Jan 4;60(3):1751-9. doi: 10.1128/AAC.02641-15.


Membrane-Bound PenA β-Lactamase of Burkholderia pseudomallei.

Randall LB, Dobos K, Papp-Wallace KM, Bonomo RA, Schweizer HP.

Antimicrob Agents Chemother. 2015 Dec 28;60(3):1509-14. doi: 10.1128/AAC.02444-15.


Exposing a β-Lactamase "Twist": the Mechanistic Basis for the High Level of Ceftazidime Resistance in the C69F Variant of the Burkholderia pseudomallei PenI β-Lactamase.

Papp-Wallace KM, Becka SA, Taracila MA, Winkler ML, Gatta JA, Rholl DA, Schweizer HP, Bonomo RA.

Antimicrob Agents Chemother. 2015 Nov 23;60(2):777-88. doi: 10.1128/AAC.02073-15. Print 2016 Feb.


Analysis of the Structure and Function of FOX-4 Cephamycinase.

Lefurgy ST, Malashkevich VN, Aguilan JT, Nieves E, Mundorff EC, Biju B, Noel MA, Toro R, Baiwir D, Papp-Wallace KM, Almo SC, Frere JM, Bou G, Bonomo RA.

Antimicrob Agents Chemother. 2015 Nov 2;60(2):717-28. doi: 10.1128/AAC.01887-15. Print 2016 Feb.


Inhibition of Klebsiella β-Lactamases (SHV-1 and KPC-2) by Avibactam: A Structural Study.

Krishnan NP, Nguyen NQ, Papp-Wallace KM, Bonomo RA, van den Akker F.

PLoS One. 2015 Sep 4;10(9):e0136813. doi: 10.1371/journal.pone.0136813. eCollection 2015.


Activity of ceftazidime/avibactam against isogenic strains of Escherichia coli containing KPC and SHV β-lactamases with single amino acid substitutions in the Ω-loop.

Winkler ML, Papp-Wallace KM, Bonomo RA.

J Antimicrob Chemother. 2015 Aug;70(8):2279-86. doi: 10.1093/jac/dkv094. Epub 2015 May 8.


Exploring the Role of Residue 228 in Substrate and Inhibitor Recognition by VIM Metallo-β-lactamases.

Mojica MF, Mahler SG, Bethel CR, Taracila MA, Kosmopoulou M, Papp-Wallace KM, Llarrull LI, Wilson BM, Marshall SH, Wallace CJ, Villegas MV, Harris ME, Vila AJ, Spencer J, Bonomo RA.

Biochemistry. 2015 May 26;54(20):3183-96. doi: 10.1021/acs.biochem.5b00106. Epub 2015 May 12.


Activities of ceftazidime, ceftaroline, and aztreonam alone and combined with avibactam against isogenic Escherichia coli strains expressing selected single β-lactamases.

Papp-Wallace KM, Bajaksouzian S, Abdelhamed AM, Foster AN, Winkler ML, Gatta JA, Nichols WW, Testa R, Bonomo RA, Jacobs MR.

Diagn Microbiol Infect Dis. 2015 May;82(1):65-9. doi: 10.1016/j.diagmicrobio.2015.02.003. Epub 2015 Feb 14.


Avibactam and inhibitor-resistant SHV β-lactamases.

Winkler ML, Papp-Wallace KM, Taracila MA, Bonomo RA.

Antimicrob Agents Chemother. 2015 Jul;59(7):3700-9. doi: 10.1128/AAC.04405-14. Epub 2015 Feb 17.


Variants of β-lactamase KPC-2 that are resistant to inhibition by avibactam.

Papp-Wallace KM, Winkler ML, Taracila MA, Bonomo RA.

Antimicrob Agents Chemother. 2015 Jul;59(7):3710-7. doi: 10.1128/AAC.04406-14. Epub 2015 Feb 9.


Unexpected challenges in treating multidrug-resistant Gram-negative bacteria: resistance to ceftazidime-avibactam in archived isolates of Pseudomonas aeruginosa.

Winkler ML, Papp-Wallace KM, Hujer AM, Domitrovic TN, Hujer KM, Hurless KN, Tuohy M, Hall G, Bonomo RA.

Antimicrob Agents Chemother. 2015 Feb;59(2):1020-9. doi: 10.1128/AAC.04238-14. Epub 2014 Dec 1.


Following drug uptake and reactions inside Escherichia coli cells by Raman microspectroscopy.

Heidari Torkabadi H, Bethel CR, Papp-Wallace KM, de Boer PA, Bonomo RA, Carey PR.

Biochemistry. 2014 Jul 1;53(25):4113-21. doi: 10.1021/bi500529c. Epub 2014 Jun 18.


Reclaiming the efficacy of β-lactam-β-lactamase inhibitor combinations: avibactam restores the susceptibility of CMY-2-producing Escherichia coli to ceftazidime.

Papp-Wallace KM, Winkler ML, Gatta JA, Taracila MA, Chilakala S, Xu Y, Johnson JK, Bonomo RA.

Antimicrob Agents Chemother. 2014 Aug;58(8):4290-7. doi: 10.1128/AAC.02625-14. Epub 2014 May 12.


Novel β-lactamase inhibitors: a therapeutic hope against the scourge of multidrug resistance.

Watkins RR, Papp-Wallace KM, Drawz SM, Bonomo RA.

Front Microbiol. 2013 Dec 24;4:392. doi: 10.3389/fmicb.2013.00392.


New β-lactamase inhibitors: a therapeutic renaissance in an MDR world.

Drawz SM, Papp-Wallace KM, Bonomo RA.

Antimicrob Agents Chemother. 2014;58(4):1835-46. doi: 10.1128/AAC.00826-13. Epub 2013 Dec 30. Review.


A kinetic analysis of the inhibition of FOX-4 β-lactamase, a plasmid-mediated AmpC cephalosporinase, by monocyclic β-lactams and carbapenems.

Papp-Wallace KM, Mallo S, Bethel CR, Taracila MA, Hujer AM, Fernández A, Gatta JA, Smith KM, Xu Y, Page MG, Desarbre E, Bou G, Bonomo RA.

J Antimicrob Chemother. 2014 Mar;69(3):682-90. doi: 10.1093/jac/dkt434. Epub 2013 Nov 13.


Non-phenotypic tests to detect and characterize antibiotic resistance mechanisms in Enterobacteriaceae.

Lupo A, Papp-Wallace KM, Sendi P, Bonomo RA, Endimiani A.

Diagn Microbiol Infect Dis. 2013 Nov;77(3):179-94. doi: 10.1016/j.diagmicrobio.2013.06.001. Epub 2013 Oct 3. Review.


Insights into β-lactamases from Burkholderia species, two phylogenetically related yet distinct resistance determinants.

Papp-Wallace KM, Taracila MA, Gatta JA, Ohuchi N, Bonomo RA, Nukaga M.

J Biol Chem. 2013 Jun 28;288(26):19090-102. doi: 10.1074/jbc.M113.458315. Epub 2013 May 8.


Design and exploration of novel boronic acid inhibitors reveals important interactions with a clavulanic acid-resistant sulfhydryl-variable (SHV) β-lactamase.

Winkler ML, Rodkey EA, Taracila MA, Drawz SM, Bethel CR, Papp-Wallace KM, Smith KM, Xu Y, Dwulit-Smith JR, Romagnoli C, Caselli E, Prati F, van den Akker F, Bonomo RA.

J Med Chem. 2013 Feb 14;56(3):1084-97. doi: 10.1021/jm301490d. Epub 2013 Feb 4.


Early insights into the interactions of different β-lactam antibiotics and β-lactamase inhibitors against soluble forms of Acinetobacter baumannii PBP1a and Acinetobacter sp. PBP3.

Papp-Wallace KM, Senkfor B, Gatta J, Chai W, Taracila MA, Shanmugasundaram V, Han S, Zaniewski RP, Lacey BM, Tomaras AP, Skalweit MJ, Harris ME, Rice LB, Buynak JD, Bonomo RA.

Antimicrob Agents Chemother. 2012 Nov;56(11):5687-92. doi: 10.1128/AAC.01027-12. Epub 2012 Aug 20.


Exploring the role of a conserved class A residue in the Ω-Loop of KPC-2 β-lactamase: a mechanism for ceftazidime hydrolysis.

Levitt PS, Papp-Wallace KM, Taracila MA, Hujer AM, Winkler ML, Smith KM, Xu Y, Harris ME, Bonomo RA.

J Biol Chem. 2012 Sep 14;287(38):31783-93. doi: 10.1074/jbc.M112.348540. Epub 2012 Jul 26.


Understanding the molecular determinants of substrate and inhibitor specificities in the Carbapenemase KPC-2: exploring the roles of Arg220 and Glu276.

Papp-Wallace KM, Taracila MA, Smith KM, Xu Y, Bonomo RA.

Antimicrob Agents Chemother. 2012 Aug;56(8):4428-38. doi: 10.1128/AAC.05769-11. Epub 2012 Jun 11.


Crystal structures of KPC-2 β-lactamase in complex with 3-nitrophenyl boronic acid and the penam sulfone PSR-3-226.

Ke W, Bethel CR, Papp-Wallace KM, Pagadala SR, Nottingham M, Fernandez D, Buynak JD, Bonomo RA, van den Akker F.

Antimicrob Agents Chemother. 2012 May;56(5):2713-8. doi: 10.1128/AAC.06099-11. Epub 2012 Feb 13.


Inactivation of a class A and a class C β-lactamase by 6β-(hydroxymethyl)penicillanic acid sulfone.

Papp-Wallace KM, Bethel CR, Gootz TD, Shang W, Stroh J, Lau W, McLeod D, Price L, Marfat A, Distler A, Drawz SM, Chen H, Harry E, Nottingham M, Carey PR, Buynak JD, Bonomo RA.

Biochem Pharmacol. 2012 Feb 15;83(4):462-71. doi: 10.1016/j.bcp.2011.11.015. Epub 2011 Dec 2.


Carbapenems: past, present, and future.

Papp-Wallace KM, Endimiani A, Taracila MA, Bonomo RA.

Antimicrob Agents Chemother. 2011 Nov;55(11):4943-60. doi: 10.1128/AAC.00296-11. Epub 2011 Aug 22. Review.


Molecular Investigations of PenA-mediated β-lactam Resistance in Burkholderia pseudomallei.

Rholl DA, Papp-Wallace KM, Tomaras AP, Vasil ML, Bonomo RA, Schweizer HP.

Front Microbiol. 2011 Jul 1;2:139. doi: 10.3389/fmicb.2011.00139. eCollection 2011.


Elucidating the role of Trp105 in the KPC-2 β-lactamase.

Papp-Wallace KM, Taracila M, Wallace CJ, Hujer KM, Bethel CR, Hornick JM, Bonomo RA.

Protein Sci. 2010 Sep;19(9):1714-27. doi: 10.1002/pro.454.


Substrate selectivity and a novel role in inhibitor discrimination by residue 237 in the KPC-2 beta-lactamase.

Papp-Wallace KM, Taracila M, Hornick JM, Hujer AM, Hujer KM, Distler AM, Endimiani A, Bonomo RA.

Antimicrob Agents Chemother. 2010 Jul;54(7):2867-77. doi: 10.1128/AAC.00197-10. Epub 2010 Apr 26.

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