Clinical Isolates of Acinetobacter spp. Are Highly Serum Resistant Despite Efficient Recognition by the Complement System

Abstract

Gram-negative bacteria from the genus Acinetobacter are responsible for life-threating hospital-related infections such as pneumonia, septicemia, and meningitis, especially in immunocompromised patients. Worryingly, Acinetobacter have become multi- and extensively drug resistant (MDR/XDR) over the last few decades. The complement system is the first line of defense against microbes, thus it is highly important to increase our understanding of evasion mechanisms used by Acinetobacter spp. Here, we studied clinical isolates of Acinetobacter spp. (n=50), aiming to characterize their recognition by the complement system. Most isolates tested survived 1 h incubation in 30% serum, and only 8 isolates had a lower survival rate, yet none of those isolates were fully killed. Intriguingly, four isolates survived in human whole blood containing all cell component. Their survival was, however, significantly reduced. Flow cytometry analyses revealed that most of the isolates were detected by human IgG and IgM. Interestingly, we could not detect any significant concentration of deposited C1q, despite observing C4b deposition that was abolished in C1q-deficient serum, indicating transient binding of C1q to bacteria. Moreover, several isolates were recognized by MBL, with C4b deposition abolished in MBL-deficient serum. C3b was deposited on most isolates, but this was not, however, seen with respect to C5b and formation of the membrane attack complex (MAC), indicating that many isolates could avoid complement-mediated lysis. India ink staining showed that isolates were capsulated, and capsule thickness varied significantly between isolates. Studies performed on a wild-type strain and capsule mutant strains, demonstrated that the production of a capsular polysaccharide is one mechanism that mediates resistance to complement-mediated bactericidal activity by preventing MAC deposition and lysis. Our data showed that most clinical Acinetobacter spp. isolates are highly serum resistant despite being efficiently recognized by the complement system.

Phenotypic and Genomic Characterization of Nine String-Positive Carbapenem-Resistant Acinetobacter baumannii Isolates from Israel

“…These results are complementary to the results on biofilm formation since biofilm formation and motility are usually mutually exclusive lifestyles in bacterial populations ( 25 ). The bacterial capsule plays a role in protecting bacteria from the environment, such as the host immune response, and serum resistance may serve as a marker of Acinetobacter virulence ( 26 – 28 ). However, as with other virulence-related phenotypes, the stCRAB isolates that we tested behaved heterogeneously.…”

Microbiological Hazard Analysis of Car Wash Wastewater

“…Phylogenetic tree for bacterial cells from a car wash: a) automatic car wash "A1" b) manual car wash " M1", c) manual car wash "M2". Bacterial groups: ▲-Firmicutes, • -Enterobacteria, ■ -Proteobacteria have become multidrug resistant [58]. One of the bacteria resistant to the commercial antibiotics is Aeromonas hydrophila which can be transmitted by bioareosols [59].…”

Anti-Acinetobacter baumannii single-chain variable fragments provide therapeutic efficacy in an immunocompromised mouse pneumonia model

“…The carbapenem-resistant Acinetobacter baumannii (CRAB) has become one of the most clinically critical pathogens in medical care due to its severe threat to human health [1,2]. Nosocomial infections, including pneumonia, bloodstream infection, urinary tract infection, and skin, soft tissue and bone infections caused by CRAB particularly threaten newborns, immunocompromised individuals, and patients hospitalized at intensive care unit (ICU) [3][4][5][6][7][8][9][10][11]. In particular, CRAB pneumonia, which has a high in-hospital mortality rate of up to 46%, has received a great deal of attention [1,12].…”

“…Antimicrobial resistance (AMR), ranking as one of the top ten health threats in the world, has severely compromised the treatment of CRAB infections, particularly its tendency to be extensively drug-resistant (XDR), only susceptible to limited antibiotics (e.g. colistin and tigecycline), and pan-resistant isolates that are resistant to all antibiotics [11,13]. Accordingly, the World Health Organization (WHO) has classi ed CRAB as a critical priority pathogen (Priority 1) for which functional antibiotics capable of combating CRAB infections are urgently needed [13].…”