Extensively Drug-Resistant Klebsiella pneumoniae Counteracts Fitness and Virulence Costs That Accompanied Ceftazidime-Avibactam Resistance Acquisition

Abstract

Extensively drug-resistant Klebsiella pneumoniae causing major outbreaks and severe infections has become a significant challenge for health care systems worldwide. Rapid resistance development against last-resort therapeutics like ceftazidime-avibactam is a significant driver for the accelerated emergence of such pathogens.

Highly Virulent and Multidrug-Resistant <i>Escherichia Coli</i> Sequence Type 58 from a Sausage in Germany

“…Highly virulent E. coli representatives are capable of causing bacteremia [21] and therefore must compete with the host defense system (e.g., the complement system). Gram-negative bacteria use several different mechanisms to deal with the immune response provided by various mechanisms, such as capsule expression [22], down-regulation of envelope stress response pathways [23], and outer membrane surface modifications [24]. Therefore, we challenged this foodborne strain by incubation in 50% human serum for four hours.…”

“…Quantification of the extent of siderophores secreted by PBIO3502 was performed according to a previously published protocol [23]. Briefly, the adjusted bacterial suspensions were diluted and grown in 5 mL of chelated M9 minimal medium supplemented with casamino acids (c-M9-CA) at 37 °C and 130 rpm for 24 hours.…”

“…Determination of survival in 50% human serum was performed as previously described [23]. Briefly, overnight cultures were diluted 1:100 in 5 mL of fresh LB and incubated with shaking at 37 °C until OD600 reached 0.…”

“…Infections of larvae of the greater wax moth G. mellonella were performed as previously described [23]. Overnight cultures were diluted 1:100 in 30 mL of fresh LB and incubated with shaking at 37 °C to an OD600 of 1.0.…”

Synthesis of Functionalized N-(4-Bromophenyl)furan-2-carboxamides via Suzuki-Miyaura Cross-Coupling: Anti-Bacterial Activities against Clinically Isolated Drug Resistant A. baumannii, K. pneumoniae, E. cloacae and MRSA and Its Validation via a Computational Approach

“…These infections have developed resistance to a broad spectrum of antibiotics, including quinolones, β-lactams, and aminoglycosides, and can only be treated with toxigenic antibiotics like polymyxin and colistin [ 4 ]. The pathogens acquired resistance by various mechanisms such as an efflux pump in A. baumannii and E. cloacae [ 5 , 6 ], porin protein loss and decreased intake of antibiotics in K. pneumoniae [ 7 ], and production of PBP2a in S. aureus [ 8 ]. The development of new anti-microbial pharmaceuticals is still in demand since diseases and previously existing antibiotic agents have a diminishing effect on microbial resistance, which are significant risk factors for morbidity and mortality in both developed and underdeveloped countries [ 9 , 10 , 11 ].…”