SUMMARY Acinetobacter is a complex genus, and historically, there has been confusion about the existence of multiple species. The species commonly cause nosocomial infections, predominantly aspiration pneumonia and catheter-associated bacteremia, but can also cause soft tissue and urinary tract infections. Community-acquired infections by Acinetobacter spp. are increasingly reported. Transmission of Acinetobacter and subsequent disease is facilitated by the organism's environmental tenacity, resistance to desiccation, and evasion of host immunity. The virulence properties demonstrated by Acinetobacter spp. primarily stem from evasion of rapid clearance by the innate immune system, effectively enabling high bacterial density that triggers lipopolysaccharide (LPS)–Toll-like receptor 4 (TLR4)-mediated sepsis. Capsular polysaccharide is a critical virulence factor that enables immune evasion, while LPS triggers septic shock. However, the primary driver of clinical outcome is antibiotic resistance. Administration of initially effective therapy is key to improving survival, reducing 30-day mortality threefold. Regrettably, due to the high frequency of this organism having an extreme drug resistance (XDR) phenotype, early initiation of effective therapy is a major clinical challenge. Given its high rate of antibiotic resistance and abysmal outcomes (up to 70% mortality rate from infections caused by XDR strains in some case series), new preventative and therapeutic options for Acinetobacter spp. are desperately needed.

The photochemistry of organosilanes was used to (1) create mixed monolayers having continuously adjustable surface free energies and (2) affect high resolution adhesion and spatial orientation of biological cells on silica substrates. Monolayers were formed from two materials, an aminoalkylsilane, NH2(CH2)2NH(CH2)3Si(OCH3)3 (EDA), and a perfluorinated alkylsilane, CF3(CF2)s(CH2)2Si(CH3)zC1 (1 3F), and were characterized by ellipsometry and water contact angle measurements. Deep UV (193 nm) radiation was used to induce photochemical changes in the cell-adhesive EDA monolayers. X-ray photoelectron spectroscopy indicated that the amine groups of EDA were removed by the exposure, leaving only Si-OH or alkyl fragments having 5 3 carbons. The exposed substrates were then reacted with 13F to form mixed monolayers or hydrophobic monolayers that inhibited cell adhesion in the irradiated regions. The degree of 13F reactivity with EDA in the unirradiated regions was observed to be solvent-dependent, suggesting that conformational states of the surface amine groups lead to a reduction in their accessibility. The selective photochemistry was exploited to produce high resolution molecular patterns, defined using patterned irradiation, that were mapped with scanning Auger electron spectroscopy. The patterns were used to spatially control the adhesion and direct the outgrowth of rat hippocampal neurons and porcine aortic endothelial cells in vitro. Patterns of controlled geometry may provide new approaches to the study of surface-directed growth, intercellular communication, and organogenesis or be used to control the alignment of individual cells with transducer elements in biosensors and implants. IntroductionRecent reports have indicated that monolayer systems can be targeted for a variety of applications, including cell adhesion and patterning.',2 Several techniques have been introduced in the past few years for the production of patterned self-assembled monolayers (SAMs) of organic functionalitie~.~~~ One approach utilizes conventional photoresist methodology to produce high resolution patterns for the adhesion and growth of cells.2 A fundamentally new technique involves direct modification of SAMs by patterned deep UV e x p o s~r e .~~~ Molecules in the exposed regions of a SAM absorb the radiation and undergo photocleavage to yield surface residues. These residues can then be modified with a second type of functionality. This technique offers several

The lethality of A. baumannii strains depends on distinct stages. Strains resistant to early innate effectors are able to establish very high early bacterial blood density, and subsequent sustained bacteremia leads to Toll-like receptor 4-mediated hyperinflammation and lethality. These results have important implications for translational efforts to develop therapies that modulate host-microbe interactions.

Inflammatory caspases (caspase-1, caspase-4, caspase-5 and caspase-11 (caspase-1/-4/-5/-11)) mediate host defense against microbial infections, processing pro-inflammatory cytokines and triggering pyroptosis. However, precise checkpoints are required to prevent their unsolicited activation. Here we report that serpin family B member 1 (SERPINB1) limited the activity of those caspases by suppressing their caspase-recruitment domain (CARD) oligomerization and enzymatic activation. While the reactive center loop of SERPINB1 inhibits neutrophil serine proteases, its carboxy-terminal CARD-binding motif restrained the activation of pro-caspase-1/-4/-5/-11. Consequently, knockdown or deletion of SERPINB1 prompted spontaneous activation of caspase-1/-4/-5/-11, release of the cytokine IL-1β and pyroptosis, inducing elevated inflammation after non-hygienic co-housing with pet-store mice and enhanced sensitivity to Reprints and permissions information is available at www.nature.com/reprints.