Lytic transglycosylases (Lts) are involved in recycling, cell division, and metabolism of the peptidoglycan. They have been understudied for their usefulness as potential antibacterial targets due to their high redundancy in Gram-negative bacteria. Bulgecin A is an O-sulphonated glycopeptide that targets primarily soluble lytic tranglycosylases (Slt). It has been shown that bulgecin A increases the efficacy of β-lactams that target penicillin bindings proteins (PBPs). Here, we present the high-resolution crystal structure of LtgA from Neisseria meningitidis strain MC58, a membrane bound homolog of Escherichia coli Slt, in complex with bulgecin A. The LtgA-bulgecin A complex reveals the mechanism of inhibition by bulgecin A at near atomic resolution. We further demonstrate that bulgecin A is not only a potent inhibitor of LtgA, but most importantly, it restores the efficacy of β-lactam antibiotics in strains of N. meningitidis and Neisseria gonorrhoeae that have reduced susceptibility to β-lactams. This is particularly relevant for N. gonorrhoeae where no vaccines are available. This work illustrates how best to target dangerous pathogens using a multiple drug target approach, a new and alternative approach to fighting antibiotic resistance.

Inequity aversion plays a central role in human cooperation. Some animals similarly show frustration and become demotivated when rewarded more poorly than a conspecific, which has been taken as evidence of inequity aversion. An alternative explanation - social disappointment - shifts the cause of frustration from the unequal reward to the human experimenter who could – but elects not to – treat subject and partner equally. This study investigates whether social disappointment could explain frustration patterns in long-tailed macaques, Macaca fascicularis. We tested twelve monkeys in a novel inequity aversion paradigm. Subjects had to pull a lever and were rewarded with low-value food; in half of the trials a partner worked alongside the subjects receiving high-value food. Rewards were distributed either by a human or a machine. In line with the social disappointment hypothesis monkeys rewarded by the human refused food more often than monkeys rewarded by the machine. Our study extends previous findings in chimpanzees and suggests that both social disappointment and food competition drive refusal patterns.

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