Insights into collateral susceptibility and collateral resistance in Acinetobacter baumannii during antimicrobial adaptation

The susceptibility of Acinetobacter baumannii exposed to primary antibiotic can be either increased or decreased when exposed to secondary antibiotic. This study was designed to assess the relative fitness, collateral susceptibility and collateral resistance of polymyxin B- (PMB-) adapted A. baumannii to ciprofloxacin (CIP), meropenem (MER), PMB, tetracycline (TET) and tobramycin (TOB). Strains of wild-type A. baumannii KACC 12454 (AB^KACC), wild-type A. baumannii CCARM 12088 (AB^CCARM), PMB-adapted AB^KACC, PMB-adapted AB^CCARM, stabilized AB^KACC and stabilized AB^CCARM were used in this study. Compared to the wild-type AB^KACC, the MICs of PMB were increased from 2 to 128 μg ml⁻¹ against PMB-adapted AB^KACC, while MICs of CIP, MER, TET and TOB were decreased from 2 to 1 μg ml⁻¹, 16 to 1 μg ml⁻¹, 16 to 2 μg ml⁻¹ and 64 to 16 μg ml⁻¹, respectively. The PMB-adapted AB^CCARM was resistant to CIP (32 μg ml⁻¹) and PMB (64 μg ml⁻¹) compared to the wild-type AB^CCARM. The resistance of stabilized AB^KACC and AB^CCARM to all antibiotics was lost after antibiotic-free culture in the exception of CIP and TET. The susceptibilities of wild-type, PMB-adapted and stabilized AB^KACC and AB^CCARM to CIP, MER, PMB, TET and TOB were increased in the presence of β-lactamase and efflux pump inhibitors. The high levels of relative fitness were observed for stabilized AB^KACC, PMB-adapted AB^CCARM and stabilized AB^CCARM. The stabilized AB^KACC and PMB-adapted AB^CCARM were highly heteroresistance to PMB and TET, respectively. The PMB-adapted AB^KACC and AB^CCARM showed various antibiotic patterns, known as collateral susceptibility and collateral resistance. The results provide useful information for designing effective antibiotic regimens that can enhance the antibiotic activity against A. baumannii infections.     

Intrarenal arterial collateral circulation.

In three cases of intrarenal arterial collateral circulation the collateral channels developed between interlobar arteries in diseased kidneys. Probably these originated in hypertrophied spiral vessels that had arisen from the interlobar arteries in the area of the minor calyces. This form of collateral circulation will undoubtedly be recognized more frequently with the increased use of magnification radiography.     

Information sharing and collateral damage

Recent studies have revealed a novel mechanism of antigen cross-presentation by intercellular peptide transfer through gap junctions, which provides new insight about how the immune system recognizes and destroys viruses and tumor cells. At the site of infection or tumorigenesis, gap junctions provide an "information-sharing" channel through which viral- and tumor-derived peptides are transferred to professional antigen-presenting cells (APCs), leading to na?ve T-cell stimulation. Similarly, gap-junction-mediated peptide transfer from infected or malignant cells to neighboring cells incurs "collateral damage" by cytotoxic T cells, thereby limiting the spread of viruses or the progression of tumors.     

Interstitial fibrosis and collateral ventilation

Interstitial fibrosis may increase resistance to collateral flow (Rcoll) because of decreased lung volume and destruction of collateral channels or it may decrease Rcoll because of emphysematous changes around fibrotic regions. In addition, if interstitial fibrosis involves a small region of lung periphery, interdependence from surrounding unaffected lung should produce relatively large changes in volume of the fibrotic region during lung inflation. We studied the effects of interstitial fibrosis on collateral airflow by measuring Rcoll at functional residual capacity (FRC) in nine mongrel dogs before and 28 days after the local instillation of bleomycin into selected lung segments. In six of these dogs Rcoll was also measured at a higher lung volume (transpulmonary pressure = 12 cmH2O above FRC pressure). Rcoll increased in fibrotic lung segments following local treatment with bleomycin. With lung inflation (high transpulmonary pressure) Rcoll fell a similar proportion in fibrotic and nonfibrotic lung regions. These observations suggest that collateral resistance increases in fibrotic segments because lung volume decreases or because collateral pathways are involved directly in the fibrotic process. Compensatory increases in collateral communications do not occur. In addition, pulmonary interdependence does not cause disproportionate increases in volume and decreases in Rcoll of the fibrotic region during lung inflation.     

Impaired collateral development in mature rats

The effect of maturation on collateral development of resistance arteries was investigated. Three to four sequential mesenteric arteries were ligated to create collateral pathways in anesthetized young (approximately 200 g) and mature (approximately 600 g) rats. Blood flow was similarly elevated in collaterals of young and mature animals. In vivo inner arterial diameter was increased only within young collaterals (33 +/- 7%, P < 0.001). Increases in number of intimal nuclei (57 +/- 10% vs. 52 +/- 14%) and cross-sectional medial area (33 +/- 13% vs. 38 +/- 5%) were similar between young and mature collaterals. Relative to the same animal controls, collateral endothelial nitric oxide synthase mRNA was increased as much in mature as in young rats. Proteomic analysis revealed significant differences in protein expression with maturation between control arteries as well as flow-loaded collateral vessels. The results indicate that, whereas intimal and medial remodeling events were similar in collaterals of young and mature rats, luminal expansion occurred only in young rats. Alteration in arterial protein expression with maturation and altered responses to stimuli for collateral development may contribute to this impairment.     

耐药细菌中交互敏感现象研究进展

细菌耐药性是全球亟待解决的重要公共卫生问题之一,耐药病原菌对人类和动物健康构成极大威胁。交互敏感性、附带敏感性(collateral sensitivity)是指耐药细菌在进化过程中出现的对一类抗菌药物耐药,而对另一类或几类抗菌药物更加敏感的现象。利用交互敏感策略限制甚至逆转细菌耐药性以恢复其对抗菌药物的敏感性是细菌耐药性研究的热点。本文综述了细菌交互敏感的最新研究进展,主要从交互敏感性的概念、表型及机制研究等方面进行阐述,以期为防控和治疗耐药病原菌感染提供新思路。     

Estrogen therapy induces collateral and microvascular remodeling

Estrogen increases proliferation and migration of cultured endothelial cells and perfusion of ischemic hindlimbs of rabbits. We tested the hypothesis that estrogen is angiogenic and arteriogenic in the heart during progressive coronary occlusion. Ovariectomized (OVX) and 17beta-estradiol (1 mg.kg(-1).wk(-1) im)-treated OVX (OVX-ES) female New Zealand White rabbits were instrumented with an ameroid occluder on a proximal coronary artery. Four weeks after implantation of an ameroid occluder, we measured myocardial perfusion with microspheres at rest and during adenosine-induced maximal vasodilation. The heart was fixed by perfusion at physiological pressure, and capillary angiogenesis and remodeling were assessed by image analysis of tissue sections in collateral-dependent myocardium. Coronary conductance was higher at rest and during maximal vasodilation in collateral-dependent myocardium of OVX-ES than OVX rabbits. Estrogen treatment increased the wall-to-lumen ratio of collateral vessels while it decreased the wall-to-lumen ratio of noncollateral arteries in normal regions. In normal and collateral-dependent myocardium, mean capillary diameter and capillary volume density were greater in OVX-ES rabbits. However, estrogen had no effect on capillary length density in either region of the myocardium. These data suggest that estrogen induces remodeling of the collateral vasculature and may stimulate growth of the resistance vessels, thereby providing protection during development of a gradual coronary occlusion.