Polymyxin Resistance and Heteroresistance Are Common in Clinical Isolates of
            <i>Achromobacter</i>
            Species and Correlate with Modifications of the Lipid A Moiety of Lipopolysaccharide

MacDonald, Lewis; Keenan, Sean; Lorenzo, Flaviana Di; Adade, Nana E; Kenna, D.; Millar, B. Cherie; Moore, John E.; Vivas, J.; Molinaro, Antonio; Valvano, Miguel A.

doi:10.1128/spectrum.03729-22

Cited by 7 publications

(5 citation statements)

References 88 publications

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“…However, the location of the sixth acyl chain remained to be confirmed. In addition, due to the detection of 15 : 0(2‐OH) in the compositional analysis, it might be also speculated that this fatty acid is present as a secondary substituent of the primary N ‐linked acyl chains of the reducing glucosamine in the penta‐acylated lipid A forms, as previously observed for other bacteria experiencing secondary 2‐hydroxylation in their lipid A [23–26] …”

Section: Resultsmentioning

confidence: 68%

“…In addition, due to the detection of 15 : 0(2-OH) in the compositional analysis, it might be also speculated that this fatty acid is present as a secondary substituent of the primary N-linked acyl chains of the reducing glucosamine in the pentaacylated lipid A forms, as previously observed for other bacteria experiencing secondary 2-hydroxylation in their lipid A. [23][24][25][26] Finally, in order to shed light on the actual presence of lipid A species decorated by two phosphate groups, and therefore lacking in the hexose decoration, the precursor ion at m/z 1753.6 was chosen as representative of the cluster ascribed to bis-phosphorylated penta-acylated lipid A species and analyzed by negative-ion MS/MS. The spectrum (Figure 5) showed an intense peak at m/z 1481.5 that matched with an ion derived by the loss of a 16 : 0(OH) unit, while two less intense peaks were detected at m/z 1401.4 and m/z 1655.5 and were assigned to ions originated from the loss of a phosphate group (for m/z 1655.5), or a 16 : 0(OH) unit and phosphate (for m/z 1401.4).…”

Section: Chembiochemmentioning

confidence: 64%

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Pushing the Boundaries of Structural Heterogeneity with the Lipid A of Marine Bacteria Cellulophaga

et al. 2023

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Marine bacteria, which are often described as chemical gold, are considered an exceptional source of new therapeutics. Considerable research interest has been given to lipopolysaccharides (LPSs), the main components of the Gram-negative outer membrane. LPS and its lipid A portion from marine bacteria are known to exhibit a tricky chemistry that has been often associated with intriguing properties such as behaving as immune adjuvants or anti-sepsis molecules. In this scenario, we report the structural determination of the lipid A from three marine bacteria within the Cellulophaga genus, which showed to produce an extremely heterogenous blend of tetra-to hexaacylated lipid A species, mostly carrying one phosphate and one D-mannose on the glucosamine disaccharide backbone. The ability of the three LPSs in activating TLR4 signaling revealed a weaker immunopotential by C. baltica NNO 15840 T and C. tyrosinoxydans EM41 T , while C. algicola ACAM 630 T behaved as a more potent TLR4 activator.

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Section: Resultsmentioning

confidence: 68%

Section: Chembiochemmentioning

confidence: 64%

Pushing the Boundaries of Structural Heterogeneity with the Lipid A of Marine Bacteria Cellulophaga

et al. 2023

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“…Strains were grown in a semi-defined mineral tryptone glycerol (MTG) medium, as previously described 53 . We used nrdA sequencing to confirm the species assignments of each strain used.…”

Section: Methodsmentioning

confidence: 99%

TheAchromobacterType 3 secretion system drives pyroptosis and immunopathology via independent activation of NLRC4 and NLRP3 inflammasomes

Turton

Parks

Zarodkiewicz

et al. 2023

Preprint

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Achromobacter species are newly recognized opportunistic, pro-inflammatory Gram-negative pathogens in immunocompromised individuals, but how they interact with the innate immune system to drive inflammation is poorly understood. We created sctV (Type 3 Secretion System baseplate) mutants in three Achromobacter clinical isolates from two species and showed that all three required the T3SS to induce cell death in human macrophages. Mutating other critical T3SS components also abolished cell death, which was restored by genetic complementation. Cell death of Achromobacter- infected macrophages was contact-dependent, enhanced by bacterial internalisation, and caused by inflammasome-dependent pyroptosis (typified by Gasdermin-D cleavage and IL-1β secretion). Macrophages deficient in the inflammasome sensors NLRC4 or NLRP3 underwent pyroptosis upon bacterial internalization but those deficient in both NLRC4 and NLRP3 did not, suggesting either sensor can mediate pyroptosis induction in a T3SS-dependent manner. Detailed analysis of the intracellular trafficking of one isolate indicated that the intracellular bacteria reside in an acidic LAMP-1/dextran- positive membrane compartment. Using an intranasal mouse infection model, we observed that Achromobacter damages lung structure and causes severe illness, contingent on a functional T3SS. Together, we demonstrate that Achromobacter species can survive phagocytosis by macrophages and promote macrophage cell death and inflammation by redundant mechanisms of pyroptosis induction.

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“…Colistin HR has been reported in several bacterial species, including Enterobacter cloacae ( 6 ), Klebsiella pneumoniae ( 7 ), Stenotrophomonas maltophilia ( 8 ), and Achromobacter species ( 9 ). It was first described in A. baumannii in 2006 ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

Prevalence and Clinical Consequences of Colistin Heteroresistance and Evolution into Full Resistance in Carbapenem-Resistant Acinetobacter baumannii

et al. 2023

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Polymyxin Resistance and Heteroresistance Are Common in Clinical Isolates of Achromobacter Species and Correlate with Modifications of the Lipid A Moiety of Lipopolysaccharide

Abstract: Achromobacter species can cause chronic and potentially severe infections in immunocompromised patients, especially in those with cystic fibrosis. Bacteria cannot be eradicated due to Achromobacter 's intrinsic multidrug resistance.

Cited by 7 publications

References 88 publications

Pushing the Boundaries of Structural Heterogeneity with the Lipid A of Marine Bacteria Cellulophaga

Pushing the Boundaries of Structural Heterogeneity with the Lipid A of Marine Bacteria Cellulophaga

TheAchromobacterType 3 secretion system drives pyroptosis and immunopathology via independent activation of NLRC4 and NLRP3 inflammasomes

Prevalence and Clinical Consequences of Colistin Heteroresistance and Evolution into Full Resistance in Carbapenem-Resistant Acinetobacter baumannii

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